Mitochondrial quality control in health and disease: Updates 2026

Zhengzhao Liu; Wenbao Hu; Lin Sun; Huafeng Liu

doi:10.1097/CM9.0000000000004169

. 2026 Jun 24;139(19):2851–2884. doi: 10.1097/CM9.0000000000004169

Mitochondrial quality control in health and disease: Updates 2026

Zhengzhao Liu ^1,², Wenbao Hu ¹, Lin Sun ^3,^✉, Huafeng Liu ^1,^✉

Editor: Xuehong Zhang

PMCID: PMC13626680 PMID: 42343697

Abstract

Mitochondria are central to cellular energy metabolism, and their functional integrity is essential for maintaining cellular homeostasis and life processes. Mitochondrial quality control (MQC) encompasses a complex network of mechanisms—including mitochondrial biogenesis, mitochondrial dynamics, mitophagy, mitochondrial proteostasis, and mitochondrial-derived vesicles—that collectively preserve the structural and functional balance of mitochondria. Recent studies have revealed that dysregulation of MQC is closely associated with a broad spectrum of diseases, such as neurodegenerative disorders, cardiovascular diseases, kidney diseases, metabolic syndrome, and cancers, highlighting its critical role in pathological processes. Despite significant progress in elucidating the molecular regulation of MQC, many aspects of its complexity and multilayered regulatory mechanisms remain unresolved. This review provides a comprehensive overview of the major molecular pathways involved in MQC and their functional alterations under physiological and pathological conditions. It emphasizes the abnormalities of MQC in various diseases and explores potential therapeutic targets. Moreover, integrating the latest research advances, this article discusses emerging treatment strategies aimed at restoring and optimizing MQC, with the goal of offering theoretical insights and clinical translation avenues for future disease prevention and management.

Keywords: Mitochondria, Mitochondrial quality control, Mitophagy, Mitochondrial dynamics, Neurodegenerative disease, Cardiovascular disease, Kidney disease, Therapeutic strategies

Introduction

Mitochondria, as semi-autonomous organelles within eukaryotic cells, occupy a central role in cellular energy metabolism and physiological regulation. Beyond their well-known function as the primary source of adenosine triphosphate (ATP) generation via oxidative phosphorylation, mitochondria are intricately involved in multiple cellular processes, including metabolic pathway modulation, redox signaling, calcium homeostasis, and apoptosis regulation. This multifaceted functionality enables mitochondria to adapt their bioenergetic and metabolic output in response to the specific demands of different cell types and organs. For instance, in cardiomyocytes, mitochondria sustain continuous and high-level energy production essential for contractile function throughout life, whereas in hepatocytes, they contribute significantly to metabolic regulation and detoxification processes.^[1] Moreover, mitochondria exhibit remarkable plasticity in stem cells and immune cells, where they dynamically reprogram their function to accommodate transitions between quiescent and proliferative states, underscoring their critical role in cellular fate decisions and immune responses.^[2,3]

The functional versatility of mitochondria is further exemplified by their participation in cellular signaling networks. Notably, the interplay between mitochondria and signaling pathways such as the p38 mitogen-activated protein kinase (MAPK) pathway influences mitochondrial biogenesis, oxidative phosphorylation efficiency, thermogenesis, and iron homeostasis. This crosstalk modulates mitochondrial responses to oxidative stress and apoptotic stimuli, thereby affecting cellular survival and adaptation mechanisms, particularly in pathological contexts such as cancer.^[4] Such regulatory interactions highlight mitochondria as pivotal hubs integrating metabolic cues with intracellular signaling to maintain cellular homeostasis.

To preserve their structural integrity and functional competence, mitochondria rely on a sophisticated set of quality control mechanisms collectively termed mitochondrial quality control (MQC). MQC encompasses mitochondrial biogenesis, mitochondrial dynamics remodeling through fusion and fission, selective autophagic degradation of damaged mitochondria (mitophagy), maintenance of mitochondrial protein homeostasis, and formation of mitochondria-derived vesicles (MDVs) [Figure 1].^[2,5] These processes operate synergistically to monitor and repair mitochondrial damage or to eliminate dysfunctional mitochondria, thereby preventing the accumulation of deleterious reactive oxygen species (ROS) and maintaining metabolic stability. The dynamic balance of mitochondrial fusion and fission, for example, not only facilitates mitochondrial distribution and turnover but also modulates apoptotic sensitivity and metabolic adaptation.^[6,7] Mitophagy acts as a critical quality control pathway by selectively targeting impaired mitochondria for lysosomal degradation, thus safeguarding cellular energy metabolism and preventing pathological states.^[7,8]

Mitochondrial quality control overview. Overview of mitochondrial quality control, including mitochondrial biogenesis, mitochondrial dynamics, mitophagy, mitochondrial-derived vesicles, and mitochondrial proteostasis. HSP60/70: Heat shock protein 60/70; ISR: Integrated stress response; LONP1: Lon protease 1; NRF1/2: Nuclear respiratory factor 1/2; PGC-1ɑ: Peroxisome proliferator-activated receptor gamma coactivator 1-alpha; TFAM: Mitochondrial transcription factor A; UPR^mt: Mitochondrial unfolded protein response.

Dysregulation of MQC mechanisms is increasingly recognized as a central contributor to the pathogenesis of a broad spectrum of diseases, including neurodegenerative disorders such as Parkinson’s disease (PD) and Alzheimer’s disease (AD), cardiovascular diseases, metabolic syndromes, chronic kidney diseases, and cancer.^[1,9–12] In neurodegeneration, impaired mitophagy and mitochondrial dysfunction lead to neuronal energy deficits and increased oxidative damage, exacerbating disease progression.^[13,14] Notably, emerging therapeutic strategies, such as the transplantation of encapsulated mitochondria, have been shown to alleviate dysfunction in models of PD, offering a novel approach to directly restore mitochondrial health.^[15] Cardiovascular pathologies, including hypertensive heart disease and heart failure, involve mitochondrial structural abnormalities, disturbed dynamics, and compromised bioenergetics, which impair cardiac function.^[16,17] Metabolic diseases such as metabolic dysfunction-associated fatty liver disease (MAFLD) and type 2 diabetes mellitus (T2DM) are characterized by mitochondrial oxidative stress, altered fatty acid β-oxidation, and impaired energy metabolism, highlighting the therapeutic potential of targeting mitochondrial pathways.^[10,18,19] Moreover, cancer cells exploit mitochondrial metabolic reprogramming and MQC alterations to support malignant transformation, immune evasion, and therapeutic resistance, positioning mitochondria as promising targets for anticancer strategies.^[20,21]

Despite significant advances in elucidating MQC mechanisms and their disease associations, several challenges remain. Current methodologies often rely on in vitro or permeabilized cell models that may not fully recapitulate the complex intracellular milieu and inter-organelle interactions influencing mitochondrial function in vivo.^[5,22] The crosstalk between mitochondria and other organelles, such as lipid droplets, peroxisomes, endoplasmic reticulum (ER), and lysosomes, is critical for coordinated metabolic regulation but remains incompletely understood.^[23–26] Furthermore, the regulatory networks underlying MQC exhibit tissue-specific and context-dependent variability, complicating the development of unified models and effective therapeutic interventions.^[10,11]

This review provides a comprehensive overview from a 2026 perspective, aiming to update the field by focusing on several cutting-edge angles that have rapidly evolved since 2023. First, we highlight the integration of advanced therapeutic pipelines, such as the evolution of high-precision mitochondrial base editors for mitochondrial DNA (mtDNA) correction^[27,28] and the application of proteolysis-targeting chimeras (PROTACs) for targeted protein degradation.^[29] Second, we discuss how single-organelle and real-time imaging technologies are revealing new dimensions of mitochondrial dynamics, including the direct observation of inter-organelle communication^[30,31] and intercellular mitochondrial transfer.^[32,33] Third, we explore the application of spatial multi-omics in systematically analyzing the mitochondrial network within tissue microenvironments. Finally, we examine emerging regulatory factors, such as MDVs^[33] and peptides, broadening the understanding of mitochondria as signaling hubs. By synthesizing these recent breakthroughs, this review aims to bridge the gap from molecular mechanisms to translational applications, offering insights into next-generation diagnostic, and therapeutic strategies for mitochondrial-related diseases.

Mechanisms of MQC

Mitochondrial biogenesis

Mitochondrial biogenesis is a fundamental cellular process involving the growth and division of pre-existing mitochondria to increase mitochondrial mass and meet cellular energy demands. This process is tightly regulated at multiple levels, including transcriptional activation of nuclear and mitochondrial genes, protein import, and lipid synthesis, ensuring the expansion and functional integrity of the mitochondrial network. The biogenesis of mitochondria is orchestrated through a complex interplay of signaling pathways and transcription factors, prominently featuring the peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α), nuclear respiratory factors (NRF1 and NRF2), and mitochondrial transcription factor A (TFAM), which collectively regulate the expression of mtDNA and mitochondrial proteins encoded by both nuclear and mitochondrial genomes [Figure 2].^[34,35]

Recent advances have elucidated the molecular machinery responsible for mitochondrial protein import, such as the translocase of the outer membrane (TOM) complex and the carrier translocase of the inner membrane (TIM22) pathway, which facilitate the integration of nuclear-encoded mitochondrial proteins essential for biogenesis.^[36] Moreover, the biogenesis process is not limited to protein synthesis but also involves the assembly of mitochondrial ribosomes (mitoribosomes), which are crucial for mitochondrial translation. The biogenesis of mitoribosomes is a highly coordinated event involving nucleus-encoded assembly factors and redox-sensitive components that may act as sensors to regulate mitochondrial translation under stress conditions.^[37]

Mitochondrial biogenesis is responsive to various physiological stimuli, including exercise, environmental stress, and developmental signals, enabling cells to adapt their metabolic capacity accordingly. For instance, in skeletal muscle, mitochondrial biogenesis supports the formation of an extensive mitochondrial reticulum that facilitates efficient substrate diffusion and energy production during endurance exercise and other metabolic challenges.^[35] The regulation of mitochondrial biogenesis extends to diverse cell types, including neurons, where local biogenesis in peripheral compartments such as axons and synapses has been proposed to meet localized energy demands, suggesting spatial heterogeneity in biogenesis mechanisms.^[38]

The signaling pathways governing mitochondrial biogenesis are multifaceted. Activation of PGC-1α is a central event, often modulated by upstream kinases and transcription factors such as CREB, which can be stimulated by pharmacological agents like catalpol and zafirlukast to promote mitochondrial biogenesis and enhance mitochondrial function in disease models.^[39,40] Additionally, mitochondrial ROS have been implicated as signaling molecules that regulate mitochondrial biogenesis, as demonstrated in embryonic models where reduction of mitochondrial ROS led to decreased biogenesis via downregulation of NRF2, PGC-1α, and TFAM.^[41]

Mitochondrial biogenesis is intricately linked with other MQC processes. Crosstalk between biogenesis and mitophagy ensures the replacement of damaged mitochondria with newly synthesized ones, a balance that is crucial in health and disease.^[42] Dysregulation of mitochondrial biogenesis has been associated with various pathologies, including neurodegenerative diseases such as PD and AD, metabolic disorders, inflammatory conditions, and organ-specific diseases such as liver fibrosis and kidney injury.^[43,44] For example, in PD models, defects in mitochondrial biogenesis driven by the repression of PGC-1α due to accumulation of the transcriptional repressor Parkin interacting substrate (PARIS) contribute significantly to mitochondrial dysfunction and neuronal loss.^[45,46] Similarly, in pulmonary fibrosis and silicosis, impaired biogenesis mediated through the PGC-1α–NRF1–TFAM axis exacerbates disease progression, highlighting the therapeutic potential of targeting biogenesis pathways.^[47]

Pharmacological and lifestyle interventions that enhance mitochondrial biogenesis have garnered attention for their therapeutic promise. Exercise is a potent inducer of biogenesis, improving mitochondrial function and systemic metabolism, with transcriptional coactivators such as transcriptional coactivator with PDZ-binding motif (TAZ) linking exercise stimuli to TFAM and biogenesis.^[48,49] Natural compounds, including polyphenols and branched-chain amino acids, have also been shown to modulate mitochondrial biogenesis signaling pathways, offering potential non-pharmacological strategies to ameliorate mitochondrial dysfunction in aging and disease.^[50,51] Furthermore, emerging mitochondrial therapeutics, including gene therapy, mitochondrial transplantation, and targeted drug delivery systems, aim to restore or enhance mitochondrial biogenesis and overall MQC.^[52]

In summary, mitochondrial biogenesis is a highly regulated, dynamic process essential for cellular energy homeostasis and adaptation to physiological and pathological stimuli. Understanding the molecular mechanisms and regulatory networks of mitochondrial biogenesis continues to expand, providing critical insights into its role in health and disease and uncovering novel avenues for therapeutic intervention targeting MQC.

Mitochondrial dynamics (fusion and fission)

Mitochondrial dynamics are fundamental to maintaining mitochondrial and cellular homeostasis by regulating mitochondrial morphology, distribution, and function. Fusion involves the merging of mitochondrial membranes, allowing content mixing, including mtDNA, proteins, and metabolites, which supports mitochondrial function and integrity. Key mediators of fusion include mitofusin 1 and 2 (MFN1, MFN2) on the outer mitochondrial membrane and optic atrophy 1 (OPA1) on the inner membrane. Conversely, fission results in mitochondrial division, facilitating MQC by segregating damaged mitochondria for degradation and enabling mitochondrial distribution during cell division. Dynamin-related protein 1 (DRP1) is the principal fission protein, recruited to mitochondria by receptors such as mitochondrial fission protein 1 (FIS1), mitochondrial fission factor (MFF), and mitochondrial dynamics protein (MID) 49/51. The balance between these opposing processes is tightly regulated and critical for cellular adaptation to metabolic demands and stress responses [Figure 3].^[53–55]

Schematic illustration of mitochondrial dynamics regulation. A membrane structure derived from the ER forms an constriction site. The DRP1 protein is recruited to mediate mitochondrial fission. Mitochondrial fusion is respectively mediated by MFN1/2 on the OMM and Opa1 on the IMM, coordinating the fusion of the outer and IMMs. DRP1: Dynamin-related protein 1; ER: Endoplasmic reticulum; Fis1: Mitochondrial fission 1 protein; IMM: Inner mitochondrial membrane; Mff: Mitochondrial fission factor; Mfn: Mitofusin; Mid: Mitochondrial dynamics protein; OMM: Outer mitochondrial membrane; Opa1: Optic atrophy 1.

Mitochondrial fusion and fission are dynamically coordinated processes that influence mitochondrial morphology from fragmented to highly interconnected networks. This dynamic remodeling is essential for maintaining mtDNA integrity, optimal bioenergetics, and ROS homeostasis. Studies in yeast models have demonstrated that balanced but reduced rates of fusion and fission are sufficient to preserve mtDNA integrity and mitochondrial function, underscoring the importance of equilibrium rather than absolute activity levels of these processes.^[56,57] Post-translational modifications, particularly protein acetylation, have emerged as key regulatory mechanisms modulating the activity of fusion and fission proteins. For example, acetylation promotes mitochondrial fission, while deacetylation enhances fusion, with sirtuin family deacetylases playing pivotal roles in this regulation, thereby linking mitochondrial dynamics to cellular metabolic states.^[58,59]

The interplay between fusion and fission extends beyond morphology to influence cellular fate decisions, including apoptosis, proliferation, and differentiation. In mesenchymal stem cells (MSCs), mitochondrial dynamics are instrumental in fate determination, with aberrant fusion or fission leading to dysfunction and impaired regenerative capacity. Similarly, in various pathological contexts such as cancer, neurodegenerative diseases, and metabolic disorders, dysregulation of mitochondrial dynamics contributes to disease progression. For instance, in colorectal cancer, enhanced mitochondrial fission promotes metabolic reprogramming that supports tumor proliferation, invasion, and chemoresistance, whereas moderate fusion can protect cells from oxidative stress-induced damage. This dual role highlights the complexity of targeting mitochondrial dynamics therapeutically.^[60–62]

In neurodegenerative diseases, mutations affecting fusion and fission proteins (e.g., MFN2, OPA1, and DRP1) disrupt mitochondrial morphology and function, contributing to neuronal loss and disease progression. Therapeutic strategies aiming to restore mitochondrial dynamics, such as antisense oligonucleotide-mediated silencing of fission factors or pharmacological modulation of fusion proteins, have shown promise in rescuing mitochondrial dysfunction in disease models. Moreover, mitochondrial dynamics are intricately linked with calcium signaling and inter-organelle communication, particularly at mitochondria-associated membranes (MAMs), further influencing neuronal health.^[63–65]

Recent studies have also uncovered novel regulatory proteins that bridge fusion and fission machineries, such as mitochondrial elongation factors (MIEF1 and MIEF2), which interact with both fusion proteins (MFN1/2) and fission components (DRP1), suggesting a coordinated mechanism for balancing mitochondrial morphology. This crosstalk adds an additional layer of complexity to the regulation of mitochondrial dynamics and presents new targets for therapeutic intervention.^[66] Furthermore, mitochondrial dynamics influence immune responses, as modulation of fusion and fission in endothelial cells can alter immunogenicity and T-cell activation, with implications for transplant biology and inflammatory diseases.^[67,68] In rheumatoid arthritis (RA), mitochondrial dysfunction is a primary driver of inflammation by activating the NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome, which leads to the release of proinflammatory cytokines such as IL-1β and pyroptosis.^[69] Furthermore, mitochondrial dysregulation critically promotes macrophage polarization towards the pro-inflammatory M1 phenotype.^[70] Targeting this mitochondria-NLRP3/macrophage axis with Osthole that restores mitochondrial homeostasis represents a promising therapeutic strategy to suppress inflammation and bone destruction.^[71,72]

In summary, mitochondrial fusion and fission are vital, interdependent processes that maintain MQC, adapt mitochondrial function to cellular needs, and influence cell fate. Dysregulation of these dynamics is implicated in a wide spectrum of diseases, including cancer, neurodegenerative disease, metabolic disorders, and immune-mediated conditions. Advances in understanding the molecular mechanisms governing fusion and fission, including post-translational modifications and novel regulatory proteins, are driving the development of targeted therapies aimed at restoring mitochondrial homeostasis and improving disease outcomes.^[54,67,73]

Mitophagy

Mitophagy, a specialized form of macroautophagy, is a crucial MQC mechanism that selectively degrades damaged or dysfunctional mitochondria to maintain cellular homeostasis. This process is essential for preserving mitochondrial integrity and function, particularly in energy-demanding cells such as neurons and cardiomyocytes. The molecular mechanisms of mitophagy involve multiple pathways, including the well-characterized ubiquitin-dependent pathway and ubiquitin-independent pathways. Upon mitochondrial damage, PTEN-induced putative kinase 1 (PINK1) accumulates on the outer mitochondrial membrane, recruiting and activating parkin RBR E3 ubiquitin protein ligase (PRKN), an E3 ubiquitin ligase, which ubiquitinates mitochondrial surface proteins to signal for autophagic degradation. However, recent studies have revealed that mitophagy can also proceed via ubiquitin-independent pathways, highlighting the complexity and redundancy of MQC systems [Figure 4].^[74–76]

Mitophagy plays a pivotal role in various physiological and pathological contexts. In cardiac tissue, mitophagy is essential for removing dysfunctional mitochondria that accumulate during ischemic stress and aging, thereby protecting cardiomyocytes from oxidative damage and apoptosis. For instance, activation of mitophagy has been shown to alleviate ischemia/reperfusion-induced microvascular damage by improving MQC, reducing oxidative stress, and sustaining endothelial cell viability and proliferation.^[77,78] Conversely, defective mitophagy contributes to cardiac frailty and heart failure by allowing the accumulation of damaged mitochondria, which exacerbate ROS production and mitochondrial dysfunction.^[79,80] The interplay between mitophagy, mitochondrial dynamics (fusion and fission), and the ubiquitin-proteasome system (UPS) further modulates mitochondrial quality, with mitochondrial fission facilitating the segregation of damaged mitochondria destined for degradation.^[81,82]

In the nervous system, mitophagy is critical for neuronal health and survival. Neurons, due to their high energy demands and complex morphology, rely heavily on efficient mitochondrial turnover. Impairments in mitophagy are implicated in the pathogenesis of neurodegenerative diseases such as PD, Alzheimer’s disease (AD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS). Mutations in PINK1 and PRKN genes cause familial forms of PD by disrupting mitophagy, leading to the accumulation of dysfunctional mitochondria and neuronal death.^[74,83,84] Moreover, mitophagy dysfunction is associated with defective mitochondrial clearance and increased oxidative stress in AD and other neurodegenerative disorders, highlighting mitophagy as a promising therapeutic target.^[85–87] Emerging evidence also suggests that mitophagy intersects with other cellular processes, such as inflammation, with mitophagy modulating inflammasome activation and thereby influencing immune responses and disease progression.^[88]

Mitophagy is not only involved in disease but also in physiological adaptations and aging. For example, mitophagy contributes to mitochondrial proteome remodeling during differentiation and metabolic shifts, and its efficiency declines with age, contributing to age-related pathologies.^[89,90] Pharmacological and lifestyle interventions, including exercise and ketogenic diets, have been shown to enhance mitophagy, improving mitochondrial quality and cellular health.^[91,92] Furthermore, novel biochemical approaches, such as chimeric autophagy-tethering compounds (ATTECs), have been developed to selectively induce mitophagy, offering potential therapeutic strategies for diseases characterized by mitochondrial dysfunction.^[93]

In various organ systems, mitophagy maintains mitochondrial homeostasis under stress conditions. In the liver, mitophagy protects against ischemia/reperfusion injury (IRI) and metabolic diseases by removing damaged mitochondria and regulating mitochondrial biogenesis.^[94,95] In skeletal muscle, mitophagy contributes to muscle mass maintenance and function, with impaired mitophagy linked to sarcopenia and obesity-related muscle decline; interventions enhancing mitophagy can mitigate these effects.^[96,97] In renal diseases, the accumulation of dysfunctional mitochondria contributes to inflammation and fibrosis, driving disease progression.^[98,99] Natural compounds (e.g., Honokiol and Sulforaphane) and traditional Chinese medicine Tongluo Yishen decoction ameliorated mitochondrial dysfunction and fibrosis by regulating oxidative stress and PINK1/PRKN-mediated mitophagy.^[100–102] These findings provide preclinical evidence that modulating specific mitophagy pathways can mitigate both acute and chronic renal damage. Additionally, mitophagy modulates mitochondrial quality in response to environmental toxins and pharmacological agents, as seen in studies involving cadmium, zinc oxide nanoparticles, and chloroquine, where mitophagy dysregulation contributes to cellular toxicity.^[103–105]

At the molecular level, mitophagy is tightly regulated by signaling pathways involving sirtuins, AMP-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR), and transcription factors such as PGC-1α, forkhead box O (FOXO), and transcription factor EB (TFEB), which coordinate mitochondrial biogenesis, autophagy, and lysosomal function.^[92,106,107] Crosstalk between mitophagy and mitochondrial dynamics ensures the selective removal of damaged mitochondria while maintaining the mitochondrial network. Moreover, alternative mitophagy pathways, such as Rab9-dependent autophagy, have been identified, expanding the understanding of MQC mechanisms.^[108,109]

Mitochondrial proteostasis

Mitochondrial proteostasis is a critical process that encompasses the synthesis, import, folding, assembly, and degradation of mitochondrial proteins to maintain mitochondrial function and cellular health. Given that the majority of mitochondrial proteins are nuclear-encoded and synthesized in the cytosol, efficient and tightly regulated import mechanisms are essential to deliver these precursors into mitochondria, where they undergo folding and maturation. Disruptions in these processes lead to proteotoxic stress within mitochondria, triggering a cascade of quality control responses to restore homeostasis or initiate organelle degradation if damage is irreparable. The mitochondrial proteostasis network includes molecular chaperones such as mitochondrial heat shock protein 70 (mtHSP70) and mtHSP60, proteases such as lon protease 1 (LONP1) and caseinolytic mitochondrial matrix peptidase proteolytic subunit (CLPP), and the UPS that surveils mitochondrial outer membrane proteins and import channels. For example, LONP1 cooperates with mtHSP70 to promote protein folding and prevent aggregation of mitochondrial matrix proteins, with its ATPase activity critical for this chaperone-like function [Figure 5].^[110–112] The mitochondrial unfolded protein response (UPR^mt) is a key signaling pathway activated upon accumulation of unfolded or misfolded proteins, leading to transcriptional upregulation of chaperones and proteases to mitigate proteotoxic stress.^[113–115] Notably, UPR^mt activation is context-dependent and can be protective or deleterious depending on the physiological or pathological state.^[116–118]

Mitochondrial protein import quality control is another crucial aspect of proteostasis. TOM complex serves as the entry gate for most precursor proteins, and its function is closely monitored to prevent clogging by misfolded or stalled precursors. Defective import leads to accumulation of precursor proteins in the cytosol or mitochondrial intermembrane space, eliciting stress responses such as the integrated stress response (ISR) and proteasomal degradation pathways.^[119–121] Post-translational modifications, such as SUMOylation of TOM40, regulate the assembly and function of the import machinery, with dysregulation implicated in neurodegenerative diseases such as AD.^[122] Furthermore, mitochondrial proteostasis is interconnected with cellular proteostasis networks, as mitochondrial import defects can cause cytosolic aggregation of mitochondrial precursor proteins and exacerbate proteotoxicity.^[123,124]

Mitochondrial proteases and chaperones not only maintain protein quality but also regulate mitochondrial dynamics, bioenergetics, and lipid metabolism. For instance, the m-ATPases associated with diverse cellular activities (AAA) protease yeast mitochondrial escape 1 (Yme1) modulates protein import via TIM22 and TIM23 pathways, respiratory chain complex function, and mitochondrial lipid biosynthesis, thereby influencing mitochondrial plasticity.^[111] The mitochondrial chaperone code, governed by post-translational modifications, fine-tunes chaperone activity and mitochondrial proteostasis, with implications for disease states.^[125] In addition, small mitochondrial proteins such as neighbor of E-R Channel LINk (NERCLIN) regulate cardiolipin homeostasis and mitochondrial ultrastructure, linking lipid metabolism to proteostasis.^[126]

Mitochondrial proteostasis dysfunction is implicated in a spectrum of diseases, including cardiomyopathies, neurodegenerative disorders, metabolic syndromes, and cancer. Mutations in genes encoding mitochondrial chaperones, proteases, and import machinery components cause mitochondrial cardiomyopathies and skeletal phenotypes, highlighting the clinical relevance of proteostasis maintenance.^[127,128] In neurodegeneration, impaired mitochondrial proteostasis exacerbates proteinopathies by disrupting bioenergetics and mitophagy, contributing to disease progression.^[129,130] In metabolic diseases such as type 2 diabetes and nonalcoholic fatty liver disease, dysregulated mitochondrial proteostasis leads to mitochondrial dysfunction and cellular stress, with therapeutic potential in targeting proteostasis pathways.^[112,131] Moreover, mitochondrial proteostasis influences aging and longevity, as interventions restoring proteostasis can improve muscle function and extend lifespan.^[132,133]

In summary, mitochondrial proteostasis is a multifaceted and dynamic process essential for mitochondrial and cellular function. It integrates protein import, folding, degradation, and stress signaling pathways to preserve mitochondrial integrity. The failure of these mechanisms underlies a broad range of pathologies, making mitochondrial proteostasis a critical focus for understanding disease mechanisms and developing therapeutic strategies.^[5,134,135]

Mitochondria-derived vesicles

MDVs represent a critical and evolutionarily conserved MQC mechanism that complements other well-known processes such as mitophagy, fusion/fission dynamics, and mitochondrial biogenesis. MDVs are small vesicles, typically ranging from 70 to 150 nm in diameter, that bud off from mitochondria under physiological conditions or in response to mild oxidative stress, selectively packaging damaged or oxidized mitochondrial proteins and lipids for degradation in lysosomes or peroxisomes [Figure 6]. This selective removal of damaged mitochondrial components via MDVs preserves mitochondrial structural and functional integrity and helps restore cellular homeostasis without necessitating the wholesale degradation of entire mitochondria.^[136,137] The biogenesis of MDVs involves complex molecular machinery, including sorting nexins such as sorting nexin 9 (SNX9), which is regulated by post-translational modifications such as lysine β-hydroxybutyrylation driven by metabolites such as β-hydroxybutyrate (BHB). This modification enhances SNX9 interaction with inner mitochondrial membrane (IMM) and matrix proteins, promoting the formation of IMM/matrix MDVs and thereby improving mitochondrial function.^[138–140] In addition, mitochondrial dynamics proteins such as DRP1, along with MIRO1/2 and MID49/51, orchestrate MDV formation through membrane protrusion and scission processes, highlighting the involvement of mitochondrial fission machinery in MDVs biogenesis.^[141]

Schematic diagram of MDVs. Mitochondria maintain functional homeostasis by generating vesicles encapsulated by either double or single membranes. RAB7/9⁺ double-membrane vesicles mediate the delivery of mitochondrial antigens to the cell surface for immune presentation. PDH⁺ double-membrane vesicles and TOMM20⁺ single-membrane vesicles enter the MVB pathway. These subsequently fuse with lysosomes for microautophagic degradation or with the plasma membrane for exocytic release as exosomes. MAPL⁺ single-membrane vesicles target peroxisomes for degradation. This diversified vesicular trafficking system enables mitochondria to regulate quality control, metabolic coordination, and interorganellar communication. DRP1: Dynamin-related protein 1; EV: Extracellular vesicle; MAPL: Mitochondrial-anchored protein ligase; MDV: Mitochondrial-derived vesicle; MHC-I: Major histocompatibility complex class I; MVB: Multivesicular body; OPA1: Optic atrophy 1; PDH: Pyruvate dehydrogenase; RAB7/9: Ras-associated binding protein 7/9; SNX9: Sorting nexin 9; TOMM20: Translocase of outer mitochondrial membrane 20.

MDVs serve multiple biological functions beyond quality control. They facilitate inter-organelle communication, notably between mitochondria and lysosomes or peroxisomes, and contribute to peroxisome de novo biogenesis. MDVs also participate in immune modulation by mediating mitochondrial antigen presentation and limiting the release of mitochondrial damage-associated molecular patterns (DAMPs), thereby modulating inflammatory responses.^[136,142] The trafficking of MDVs to lysosomes is tightly regulated by adaptor proteins such as toll interacting protein (TOLLIP), which coordinates PRKN-dependent endosomal sorting of MDVs, ensuring efficient delivery and degradation of damaged mitochondrial cargo.^[143] This pathway is distinct from canonical mitophagy and can act as a first line of defense against oxidative stress by selectively removing mitochondrial components before mitophagy is triggered.^[137] In pathological contexts, dysregulation of MDV formation or trafficking has been implicated in neurodegenerative diseases, cardiovascular diseases, and cancer. For example, enhanced MDV production has been observed in autophagy-deficient cancer cells as a compensatory mechanism to maintain mitochondrial homeostasis.^[109,144] Moreover, MDVs have been linked to protection against hypoxic injury in cardiomyocytes by inhibiting mitochondrial apoptosis via B-cell lymphoma 2 (Bcl-2)-containing MDVs, suggesting therapeutic potential in ischemic heart disease.^[145,146]

Emerging evidence also suggests that MDVs contribute to the formation of extracellular vesicles (EVs) containing mitochondrial components, which play roles in intercellular communication and systemic signaling. These mitochondrial extracellular vesicles (mitoEVs) can transfer mtDNA, proteins, and even intact mitochondria between cells, influencing recipient cell metabolism, immune responses, and tissue regeneration.^[147,148] The heterogeneity of MDVs and mitoEVs, including subtypes such as mitovesicles, mitophers, and mitolysosomes, underscores their diverse physiological and pathological roles. For instance, platelet-derived EVs containing mitochondria modulate neutrophil function and inflammatory responses, highlighting the immunomodulatory capacity of mitochondrial cargo transfer.^[149] Furthermore, metabolic regulation of MDV biogenesis by metabolites such as BHB links cellular metabolic status to MQC, providing a mechanistic basis for metabolic interventions in mitochondrial dysfunction.^[138,139]

Despite these advances, several aspects of MDV biology remain incompletely understood. The precise molecular signals dictating cargo selection, the full spectrum of MDV subtypes, and their distinct trafficking routes require further elucidation. Moreover, the interplay between MDVs and other MQC pathways, such as mitophagy and UPR^mt, and their collective impact on cellular homeostasis and aging are active areas of investigation.^[114,150] Understanding the regulatory networks governing MDVs formation and function holds promise for developing novel diagnostic biomarkers and therapeutic strategies targeting mitochondrial dysfunction in a range of diseases including neurodegeneration, cardiovascular disorders, and metabolic syndromes.^[151,152] In summary, MDVs are versatile MQC entities that maintain mitochondrial and cellular health by selectively removing damaged components, mediating organelle crosstalk, and facilitating intercellular communication, thereby representing a critical frontier in mitochondrial biology and disease therapeutics.

Nuclear–mitochondria crosstalk in genome maintenance and signaling

Nuclear–mitochondrial crosstalk is central to coordinating mitochondrial genome (mtDNA) stability and cellular fate.^[153] This interaction is achieved through multi-layered mechanisms, including mitochondrial targeting of nuclear-encoded proteins, transmission of stress signals, and epigenetic regulation.

The specific import of nuclear-encoded DNA repair proteins into mitochondria constitutes the first line of defense for maintaining mtDNA integrity. For instance, the base excision repair (BER) pathway, crucial for clearing oxidative damage to mtDNA, relies on a full set of enzymes encoded by the nuclear genome and transported to the mitochondria.^[154] Defects in this nuclear-encoded, mitochondrial-targeted repair system led to accumulation of mtDNA damage, dysfunction of the electron transport chain, and a vicious cycle of elevated ROS. This is particularly prominent in metabolically active cells like neurons and is closely associated with neurodegenerative diseases.^[155,156] Furthermore, TFAM is not only essential for mtDNA packaging and transcription but also critical for maintaining mtDNA stability and integrity.^[157]

When mitochondrial function is compromised, cells initiate signaling pathways such as the ISR for communication and adaptation. For example, in non-tuberculous mycobacterial (NTM) infection, impaired mitochondrial function in macrophages is linked to attenuated expression of peroxisome PGC-1α and TFAM. Restoring their expression can remodel mitochondrial function and enhance immune response.^[158] This reveals a mechanism by which nuclear factors sense mitochondrial status to globally regulate cellular metabolism and defense.

In recent years, mitochondria-derived peptides (MDPs) have emerged as a novel class of signaling molecules, adding a new dimension to nuclear-mitochondrial dialog. These small peptides encoded by mtDNA (e.g., Humanin^[159] and mitochondrial open reading frame (ORF) of the 12S ribosomal RNA (rRNA) type-c [MOTS-c]^[160]) can be released into the cytoplasm or extracellular space, influencing nuclear gene expression networks related to metabolism, stress response, and aging. Although not directly explored in the current retrieved literature, they represent a significant emerging research direction in this field.

Genetic and epigenetic mechanisms work together to finely regulate this interactive network. At the genetic level, mutations in nuclear genes encoding MQC proteins can directly disrupt mtDNA stability. For instance, specific mtDNA mutations and haplotype polymorphisms are closely associated with metabolic reprogramming and malignant progression in thyroid cancer.^[161,162] At the epigenetic level, chemical modifications of mtDNA itself (e.g., methylation) and epigenetic regulation of nuclear MQC genes play crucial roles. In diabetic retinopathy, hyperglycemia leads to DNA hypermethylation of the mtDNA-encoded long non-coding RNA CytB (LncCytB). Its downregulated expression subsequently impairs mitochondrial genomic stability and function, a process that can be reversed by DNA methyltransferase inhibitors.^[163] This clearly defines the direct role of epigenetic dysregulation in linking metabolic disorders to mitochondrial dysfunction. Concurrently, methylation of nuclear DNA or histone modifications may regulate the expression of nuclear genes involved in MQC, such as BER enzymes and TFAM, thereby indirectly affecting mitochondrial homeostasis.

In summary, the nucleus and mitochondria form a dynamic, integrated regulatory network through protein translocation, signal transduction, and epigenetic programming. Dysregulation of this network, whether due to genetic mutations or epigenetic alterations, disrupts mtDNA stability and drives various pathological processes, including cancer,^[164,165] neurodegenerative diseases,^[155,156] and complications of metabolic diseases.^[166,167] A deeper understanding of this interaction mechanism will provide new strategies for treating related diseases by restoring nuclear-mitochondrial communication.

Other important mechanisms regulating mitochondrial function

Beyond the classical pathways of MQC, a multitude of additional mechanisms intricately regulate mitochondrial function to maintain cellular homeostasis and respond to physiological and pathological stimuli. One critical layer of regulation involves the modulation of mitochondrial dynamics and morphology by protein complexes such as the BBSome, which controls mitochondrial fission through regulation of DRP1 phosphorylation and localization. Disruption of the BBSome leads to mitochondrial hyperfusion and impaired mitochondrial respiration, highlighting the importance of precise control over mitochondrial morphology for optimal function.^[168] Similarly, MFN2 plays a pivotal role not only in mitochondrial fusion but also in maintaining MAMs between mitochondria and the ER. MFN2 deficiency disrupts MAM integrity, leading to mitochondrial fragmentation, impaired calcium homeostasis, and activation of ER stress responses, which collectively contribute to pathological remodeling such as cardiac dysfunction and neurodegeneration.^[169,170] The MAMs themselves serve as crucial hubs for inter-organelle communication, regulating lipid and ion transfer, signaling pathways, and mitochondrial dynamics. Proteins such as mitochondrial LONP1 have been identified as novel MAM tethers that coordinate MAM integrity and mitochondrial function, with their deficiency causing mitochondrial fragmentation and metabolic reprogramming.^[171]

Mitochondrial function is also modulated by the interaction with other cellular components, such as the cytoskeleton and plasma membrane. For instance, palmitoylated cytoskeleton-associated protein 4 (CKAP4) binds to mitochondrial porin voltage-dependent anion-selective channel protein 2 (VDAC2) at ER-mitochondria contact sites, regulating mitochondrial calcium uptake and membrane potential, thereby influencing oxidative phosphorylation and cellular proliferation.^[172]

At the molecular level, mitochondrial protein homeostasis is maintained by a network of chaperones, proteases, and ubiquitin-dependent degradation pathways. The mitochondrial protein import machinery acts as a sentinel for mitochondrial function, with impaired import triggering quality control responses including mitochondrial-associated degradation (MAD) and crosstalk with ER-associated degradation (ERAD) systems. These pathways ensure the removal of misfolded or mislocalized proteins, preserving mitochondrial proteome integrity and function.^[5,120,173] In addition, mitochondrial RNA quality control mechanisms, mediated by pentatricopeptide repeat (PPR) proteins, regulate mitochondrial transcript processing, editing, and decay, which are essential for proper mitochondrial gene expression and function.^[174]

Mitochondrial function is further influenced by signaling pathways involving mitochondrial receptors for hormones and intracellular mediators. Mitochondria express functional receptors for estrogen, androgen, glucocorticoids, serotonin, melatonin, cannabinoids, and purinergic signals, allowing them to respond autonomously to extracellular and intracellular cues. These signaling pathways modulate mitochondrial ROS production, bioenergetics, and activation of inflammasomes such as NLRP3, thereby linking mitochondrial function to immune responses and cellular stress adaptation.^[175–177] For example, volume-regulated anion channels (VRACs) modulate mitochondrial adaptation during macrophage activation, influencing inflammasome activity and innate immunity.^[176]

Mitochondrial transfer between cells, either via tunneling nanotubes or VEs, represents another important mechanism regulating mitochondrial function at the tissue level. Horizontal mitochondrial transfer has been observed in various physiological and pathological contexts, including cancer progression, tissue repair, and immune responses. This intercellular exchange can restore mitochondrial function in damaged cells and modulate cellular metabolism and survival, suggesting therapeutic potential for mitochondrial transplantation strategies.^[178,179]

Moreover, mitochondrial metabolites and post-translational modifications play significant roles in fine-tuning mitochondrial activity. For instance, hydrogen sulfide (H₂S) modulates mitochondrial dynamics and function through persulfidation of mitochondrial fission regulators, thereby influencing cellular processes such as cytotrophoblast invasion and neuroprotection.^[180,181] Similarly, nucleotide pool sanitization enzymes like MTH1 protect mtDNA from oxidative damage, maintaining mitochondrial integrity and platelet function.^[182] The interaction of mitochondrial proteins with metabolites such as genistein, which inhibits adenine nucleotide translocase-2, further exemplifies the complex regulation of mitochondrial bioenergetics and cellular differentiation.^[183]

Finally, mitochondrial homeostasis is tightly linked to cellular stress responses and transcriptional regulation. Transcription factors such as Kruppel-like factors (KLFs) regulate mitochondrial biogenesis, dynamics, mitophagy, and unfolded protein responses, integrating MQC with broader cellular programs.^[184] The heat shock response factor HSF1 also contributes to mitochondrial homeostasis, mediating protective signaling that preserves mitochondrial function under stress.^[185]

Collectively, these diverse mechanisms highlight the multifaceted regulation of mitochondrial function beyond classical quality control pathways. They underscore mitochondria as dynamic organelles integrated within cellular networks, capable of responding to metabolic, signaling, and environmental cues to maintain cellular and organismal health. Understanding these regulatory layers offers promising avenues for therapeutic interventions targeting mitochondrial dysfunction in a wide spectrum of diseases.

The Role of MQC in Health

Maintaining cellular energy metabolism

Mitochondria are fundamental organelles responsible for maintaining cellular energy metabolism, primarily through the production of ATP via oxidative phosphorylation. This bioenergetic function is essential for supporting diverse cellular processes and overall homeostasis. The integrity and quality of mitochondria are preserved by MQC mechanisms, which encompass mitochondrial biogenesis, dynamics (fusion and fission), mitophagy, and proteostasis and MDVs. These mechanisms ensure the removal of damaged mitochondria, maintenance of mitochondrial morphology, and adaptation to metabolic demands, thereby sustaining efficient energy production.^[186] For instance, in highly energy-dependent cells such as neurons and cardiomyocytes, MQC is critical to meet their substantial ATP requirements and to prevent dysfunction that can lead to neurodegenerative or cardiovascular diseases.^[187,188] Disruption of MQC results in accumulation of dysfunctional mitochondria, impaired ATP synthesis, and increased ROS, which exacerbate cellular damage and metabolic imbalance.^[189,190]

At the molecular level, mitochondrial dynamics modulate energy metabolism by regulating mitochondrial morphology and distribution to optimize bioenergetic efficiency. Fusion processes enhance mitochondrial connectivity and facilitate the exchange of mitochondrial contents, supporting respiratory capacity, while fission segregates damaged mitochondria for removal via mitophagy.^[191,192] The balance of these dynamics is tightly regulated and linked to metabolic states; for example, disturbances in fusion–fission equilibrium impair energy metabolism and contribute to diseases such as diabetes and cancer.^[193,194] Moreover, mitochondrial biogenesis, governed by transcriptional coactivators such as PGC-1α and signaling pathways including AMPK, replenishes the mitochondrial pool to meet increased energy demands.^[195,196] AMPK activation not only promotes mitochondrial biogenesis but also enhances mitophagy, thereby coordinating energy supply with mitochondrial quality.^[195]

Mitochondrial membrane potential (MMP) serves as a critical indicator of mitochondrial health and is integral to ATP synthesis. Beyond its canonical role, MMP functions as a dynamic signaling hub that modulates ROS production, calcium handling, and local MQC, thus influencing cellular energy homeostasis and adaptive responses.^[196] Calcium uptake by mitochondria via the mitochondrial calcium uniporter (MCU) further regulates energy metabolism by stimulating dehydrogenases in the tricarboxylic acid cycle, linking intracellular signaling to mitochondrial ATP production.^[197] Dysregulation of mitochondrial calcium homeostasis disrupts energy metabolism and is implicated in tumorigenesis and other pathologies.^[197]

Inter-organelle communication, especially between mitochondria and lipid droplets, ER, and the nucleus, is crucial for coordinating energy metabolism. Lipid droplet-mitochondria contacts facilitate the transfer of fatty acids for β-oxidation, thereby regulating energy supply and redox balance.^[23,198] Similarly, MAMs between ER and mitochondria mediate calcium transfer and lipid metabolism, influencing mitochondrial bioenergetics and cellular energy homeostasis.^[199] Furthermore, mitochondrial nuclear signaling pathways modulate the expression of genes involved in mitochondrial function and energy metabolism, ensuring coordinated cellular responses to metabolic stress.^[200]

In various physiological and pathological contexts, mitochondrial energy metabolism is dynamically regulated. For example, in adipose tissue, MQC maintains metabolic homeostasis and prevents obesity-related metabolic diseases by regulating energy expenditure and substrate metabolism.^[201] In the liver, mitochondrial dysfunction contributes to MAFLD, while interventions targeting mitochondrial quality and energy metabolism, such as herbal compounds from Poria cocos or Polygonum cuspidatum, have shown promise in restoring mitochondrial function and energy homeostasis.^[18,202] Similarly, in skeletal muscle, mitochondrial dynamics modulate energy metabolism to adapt to contraction and metabolic demands.^[192] In the brain, mitochondrial energy metabolism supports synaptic function and neuronal viability, with MQC mechanisms being essential to prevent neurodegenerative diseases.^[187,203]

Pharmacological modulation of mitochondrial energy metabolism and quality control is emerging as a therapeutic strategy. For instance, melatonin enhances mitochondrial biogenesis and mitophagy, improving energy supply under pathological conditions.^[204] Small molecules targeting mitochondrial complex I have been shown to restore energy homeostasis and reduce pathological protein accumulation in neurodegenerative disease models.^[205] Moreover, modulation of mitochondrial function influences responses to metabolic stress, as observed in diabetes and cardiovascular diseases, where improving mitochondrial bioenergetics alleviates disease progression.^[190,206]

In summary, maintaining cellular energy metabolism relies on the intricate regulation of MQC pathways that preserve mitochondrial integrity, dynamics, and function. These processes ensure efficient ATP production, redox balance, and metabolic flexibility, which are vital for cellular health and adaptation to physiological demands. Disruptions in MQC and energy metabolism underlie numerous diseases, highlighting the importance of targeting these pathways for therapeutic interventions.

Antioxidant and anti-apoptotic effects

MQC is critically influenced by the balance between oxidative stress and apoptosis, with antioxidant mechanisms playing a central role in maintaining mitochondrial integrity and cellular survival. A wide array of studies has demonstrated that natural compounds, pharmacological agents, and endogenous proteins exert protective effects against mitochondrial dysfunction by mitigating ROS accumulation and inhibiting mitochondria-mediated apoptosis pathways.

Several natural antioxidants have been shown to alleviate oxidative stress-induced mitochondrial damage and apoptosis. For instance, dioscin, a steroidal saponin, effectively reduces oxidative stress markers such as superoxide anion (O₂⁻) and hydrogen peroxide (H₂O₂), enhances antioxidant enzyme activities including superoxide dismutase (SOD) and catalase (CAT), and downregulates pro-apoptotic proteins such as Bax, cytochrome c, and caspases in diabetic nephropathy models, thereby preserving mitochondrial respiratory chain function and improving mitophagy and mitochondrial dynamics.^[207] Similarly, blueberry anthocyanin extract (BAE) mitigates arsenic-induced cognitive impairment by restoring antioxidant capacity, reducing ROS, and normalizing mitochondrial biogenesis and dynamics through modulation of PGC-1α and SIRT1 pathways.^[208] Vitamin K2 also demonstrates neuroprotective effects by suppressing mitochondrial depolarization and ROS accumulation, regulating mitochondrial fusion/fission proteins MFN1/2 and DRP1, and promoting mitophagy via the PINK1/PRKN pathway.^[209] These findings underscore the importance of antioxidant compounds in maintaining MQC and preventing apoptosis.

Pharmacological agents with antioxidant properties further exemplify the therapeutic potential of targeting mitochondrial oxidative stress. Dexmedetomidine (DEX) ameliorates hepatic IRI by restoring MMP, enhancing ATP production, reducing oxidative stress, and inhibiting apoptosis, effects mediated through upregulation of sirtuin 3 (SIRT3) and modulation of mitochondrial dynamics proteins such as DRP1 and OPA1.^[210] Telmisartan and losartan, angiotensin II receptor blockers with antioxidant activity, improve post-thaw sperm quality by enhancing mitochondrial function, increasing antioxidant enzyme levels (GPX, SOD), reducing lipid peroxidation, and decreasing apoptosis.^[211,212] Similarly, Mito-Tempo and berberine protect rabbit sperm during cryopreservation by reducing ROS and apoptosis while improving mitochondrial activity.^[213] These agents highlight the role of mitochondrial-targeted antioxidants in preserving mitochondrial integrity and preventing apoptosis in diverse biological contexts.

Endogenous mitochondrial proteins also contribute to antioxidant defense and apoptosis regulation. Mitochondrial sirtuins, particularly SIRT3, maintain mitochondrial function by activating antioxidant enzymes like manganese-dependent superoxide dismutase (MnSOD), inhibiting ROS generation, and suppressing apoptosis through FOXO and p53 pathways.^[214] The mitochondrial enzyme cytochrome c oxidase subunit 5A (COX5A) protects against doxorubicin-induced cardiotoxicity by reducing oxidative stress, preserving mitochondrial function, and inhibiting cardiomyocyte apoptosis via the phosphoinositide 3 (PI3K)/protein kinase B (AKT) signaling pathway.^[215] SIRT4 modulates mitochondrial dynamics and oxidative stress in retinal Müller glial cells, reducing apoptosis by balancing mitochondrial fusion/fission proteins and decreasing ROS levels.^[216] Moreover, hexokinase domain component 1 (HKDC1), a mitochondrial enzyme, protects against calcium oxalate nephrolithiasis by modulating oxidative stress, apoptosis, and mitochondrial function.^[217] These mitochondrial proteins are integral to the antioxidant and anti-apoptotic machinery that sustains mitochondrial quality.

Mechanistically, the interplay between oxidative stress and mitochondrial apoptosis involves modulation of MMP, release of pro-apoptotic factors such as cytochrome c, and activation of caspases. Many studies report that antioxidants restore MMP, reduce ROS, and inhibit the mitochondrial apoptotic cascade. For example, melatonin reduces ROS and Bax/Bcl-2 ratio, preventing cytochrome c release and caspase activation in various cell types.^[218] Similarly, paeonol, transported into mitochondria via translocater protein (TSPO), alleviates dexamethasone-induced mitochondrial abnormalities and apoptosis by enhancing antioxidant capacity and suppressing pro-apoptotic proteins.^[219] The mitochondrial antioxidant SS-31 scavenges ROS, stabilizes mitochondrial dynamics, and inhibits apoptosis and pyroptosis in nucleus pulposus cells.^[220] These findings illustrate that antioxidant-mediated preservation of mitochondrial function is crucial to preventing apoptosis.

Furthermore, oxidative stress-induced mitochondrial dysfunction is implicated in various pathological conditions, including neurodegeneration, cardiovascular diseases, reproductive dysfunction, and cancers. Many studies demonstrate that antioxidants and MQC modulators can reverse or attenuate mitochondrial damage and apoptosis in these contexts. For example, astaxanthin protects neurons from oxidative damage and apoptosis by restoring mitochondrial function,^[221] while hyperoside protects osteoblasts from phthalate-induced oxidative stress and apoptosis by enhancing mitophagy and activating Nrf2/HO-1 pathways.^[222] In cancer models, compounds such as manoalide and nigericin induce apoptosis via oxidative stress and mitochondrial dysfunction, highlighting the therapeutic potential of modulating mitochondrial oxidative balance.^[223,224]

In summary, the antioxidant and anti-apoptotic effects are fundamental components of MQC. Antioxidants, whether natural compounds, pharmacological agents, or endogenous mitochondrial proteins, mitigate ROS accumulation, preserve MMP, regulate mitochondrial dynamics, and inhibit the intrinsic apoptotic pathway. These mechanisms collectively maintain mitochondrial integrity and cellular homeostasis, offering promising therapeutic avenues for diseases characterized by mitochondrial dysfunction and oxidative stress-mediated apoptosis.

Imbalance of MQC and Its Association with Diseases

MQC and neurodegenerative diseases

MQC is a critical cellular system that maintains mitochondrial integrity and function, which is particularly vital in neurons due to their high energy demands and complex morphology. Neurodegenerative diseases (NDDs), including AD, PD, HD, and ALS, are characterized by progressive neuronal loss and dysfunction, with mitochondrial dysfunction emerging as a central pathological hallmark. MQC encompasses multiple interconnected processes such as mitochondrial biogenesis, dynamics (fusion and fission), mitophagy, proteostasis, and MDVs, all of which coordinate to surveil, repair, or eliminate damaged mitochondria to preserve cellular homeostasis.^[225,226] Impairment in any of these pathways leads to the accumulation of dysfunctional mitochondria, bioenergetic deficits, increased ROS production, and activation of neuroinflammatory cascades, all contributing to neurodegeneration.

In AD, for example, dysregulation of MQC manifests as impaired mitophagy and mitochondrial dynamics, leading to defective clearance of damaged mitochondria and bioenergetic failure. The mitochondrial-associated membranes (MAMs), which mediate communication between mitochondria and the ER, play a pivotal role in regulating MQC and are disrupted in AD, exacerbating mitochondrial dysfunction and neuronal loss.^[227,228] Similarly, in PD, mutations in genes such as PINK1 and PRKN, which are central regulators of mitophagy, compromise MQC and lead to the accumulation of damaged mitochondria, triggering dopaminergic neuron degeneration.^[226,229] These genetic insights underscore the importance of MQC in maintaining neuronal health and reveal potential molecular targets for intervention.

Moreover, mitochondrial proteostasis maintained by mitochondrial-resident AAA+ proteases is essential for degrading damaged mitochondrial proteins and preventing proteotoxic stress. Failure of these proteases contributes to mitochondrial dysfunction observed in various NDDs.^[230] The UPR^mt is another adaptive response activated upon mitochondrial stress to restore proteostasis by upregulating chaperones and proteases; its modulation has shown therapeutic potential in models of AD, PD, HD, and ALS.^[114] Beyond neurons, MQC in glial cells, including microglia and astrocytes, also influences neurodegeneration by affecting neuroinflammation and neuronal support, highlighting the cell-type-specific complexity of MQC in the brain.^[231]

Therapeutic strategies targeting MQC pathways have gained considerable attention. Pharmacological agents that enhance mitophagy, stabilize mitochondrial dynamics, or activate UPR^mt show promise in preclinical models by restoring mitochondrial function and slowing disease progression.^[232,233] In addition, mitochondrial-targeted drug delivery systems, such as nanoparticles and peptides, are being developed to improve the efficacy and specificity of therapeutics aimed at mitochondrial dysfunction in NDDs.^[234] Nutritional supplementation with cofactors essential for mitochondrial function, including Coenzyme Q10, B-vitamins, and antioxidants, has also been explored as adjunctive therapy.^[235]

Advanced neuroimaging techniques, such as positron emission tomography (PET) using specific tracers, enable in vivo assessment of mitochondrial oxidative stress and dysfunction, facilitating early diagnosis and monitoring of therapeutic responses in neurodegenerative disorders.^[236,237] Furthermore, emerging research highlights the role of mitochondrial retrograde signaling in modulating nuclear gene expression in response to mitochondrial dysfunction, offering additional molecular targets for intervention.^[238]

In summary, MQC dysfunction is a convergent mechanism underlying the pathogenesis of major neurodegenerative diseases. The intricate balance of mitochondrial biogenesis, dynamics, proteostasis, mitophagy, and inter-organelle communication is essential for neuronal survival and function. Disruption of these processes leads to mitochondrial damage accumulation, oxidative stress, and neuroinflammation, driving neurodegeneration. Understanding the molecular details of MQC pathways and their dysregulation in disease states provides a foundation for developing targeted therapies that restore mitochondrial integrity, offering hope for effective treatment of neurodegenerative diseases.

MQC and cardiovascular diseases

MQC plays a pivotal role in the maintenance of cardiovascular health by preserving mitochondrial integrity and function in cardiomyocytes and vascular cells, which are highly dependent on mitochondrial ATP production to meet their substantial energy demands. Cardiovascular diseases (CVDs), including IRI, heart failure, hypertrophy, atherosclerosis, hypertension, and diabetic cardiomyopathy, have been closely linked to mitochondrial dysfunction characterized by impaired oxidative phosphorylation, excessive ROS generation, disrupted calcium homeostasis, and activation of cell death pathways.^[239–241] MQC ensures the removal of damaged mitochondria and the replenishment of healthy ones, thereby maintaining cellular homeostasis in the cardiovascular system.^[242,243]

In the pathogenesis of CVDs, dysregulation of MQC processes leads to the accumulation of dysfunctional mitochondria, which exacerbates oxidative stress and inflammatory responses, contributing to cardiomyocyte death and cardiac remodeling.^[239,244] For instance, aberrant mitochondrial fission mediated by DRP1 is an early marker of mitochondrial injury and promotes cardiomyocyte apoptosis, while reduced mitochondrial fusion, regulated by MFN1/2 and OPA1, is linked to mitochondrial fragmentation and impaired bioenergetics in stressed hearts.^[243,245] Mitophagy, the selective autophagic clearance of damaged mitochondria, is generally protective by preventing the propagation of mitochondrial dysfunction; however, excessive or insufficient mitophagy can be maladaptive, contributing to cardiac injury.^[242,246] Moreover, mitochondrial biogenesis, regulated by transcriptional coactivators such as PGC-1α, is essential for restoring mitochondrial mass and function after injury, and its impairment is associated with heart failure and ischemic cardiomyopathy.^[245,247]

Emerging evidence highlights the interplay between MQC and signaling pathways such as the Hippo pathway, which modulates mitochondrial dynamics and mitophagy, influencing cardiomyocyte survival and cardiac regeneration.^[248] Additionally, posttranslational modifications of mitochondrial proteins and mitochondrial proteostasis mechanisms, including chaperones and proteases, contribute to MQC and are critical for cardiac function.^[188,249] Environmental factors, such as air pollution and mechanical stress, have been shown to impair.

MQC and acute and chronic kidney diseases

MQC plays a pivotal role in maintaining renal cellular homeostasis and function, given the kidney’s high mitochondrial density and energy demands. Acute kidney injury (AKI) and chronic kidney disease (CKD) are characterized by disrupted MQC mechanisms, which contribute to disease pathogenesis and progression.^[250] In AKI and CKD, mitochondrial dysfunction arises from maladaptive repair processes in mitochondria-rich renal tubular cells, where impaired mitochondrial bioenergetics, biogenesis, dynamics (fusion and fission), and mitophagy lead to cellular injury and death.^[251–254] The dynamic balance of mitochondrial fusion and fission is critical; excessive fission results in mitochondrial fragmentation, promoting oxidative stress and apoptosis, while impaired fusion disrupts mitochondrial networking, further exacerbating injury.^[255–257] Mitophagy, the selective autophagic removal of damaged mitochondria, is essential in AKD to prevent the accumulation of dysfunctional mitochondria and subsequent ROS production.^[258,259] Defective mitophagy has been implicated in acute tubular injury and maladaptive repair, with key regulators such as PINK1 and PRKN being promising therapeutic targets.^[260–262] Pharmacological agents such as resveratrol, L-carnitine, and apelin have demonstrated efficacy in modulating MQC proteins (Pink1, PRKN, BNIP3, DRP1, and PGC-1α), reducing oxidative stress and improving renal ATP levels in AKI models.^[259,263] Moreover, serotonin receptor agonists have emerged as novel modulators of mitochondrial biogenesis and homeostasis, offering potential therapeutic avenues in AKI and CKD by restoring mitochondrial function.^[264]

In CKD, persistent mitochondrial dysfunction contributes to progressive renal fibrosis and functional decline. Imbalances in mitochondrial dynamics favoring fission over fusion lead to mitochondrial fragmentation, oxidative stress, and inflammation, which are central to CKD pathophysiology.^[265,266] Epigenetic regulators such as SIRT6 and GLIS1 modulate mitochondrial biogenesis and dynamics via PGC-1α, attenuating oxidative damage, inflammation, and fibrosis, thereby delaying CKD progression and kidney aging.^[267,268] Mitophagy also plays a dual role in CKD; while its activation removes damaged mitochondria and limits ROS-mediated injury, dysregulated mitophagy can exacerbate fibrosis and tubular cell apoptosis.^{[261,269,270]} The interplay between mitophagy and ferroptosis, a form of iron-dependent cell death, is increasingly recognized in renal fibrosis, where mitophagy receptors such as NIP3-like protein X (NIX) inhibit ferroptosis by modulating cystine/glutamate antiporter activity.^[269] Additionally, mitochondrial dysfunction in podocytes and tubular epithelial cells disrupts energy metabolism and promotes inflammation, contributing to diabetic kidney disease (DKD) and other CKDs.^[271,272] Recent studies highlight the role of MQC in modulating immune responses and inflammation in the kidney, with autophagy and mitophagy attenuating inflammatory cascades and cell death pathways during injury and repair.^[273] The ROS accumulation caused by MQC dysfunction is also an important factor contributing to the development of DKD.^[274,275]

Experimental models of IRI demonstrate that ischemia duration and reperfusion time critically influence mitochondrial quality, with prolonged ischemia causing bioenergetic failure, disrupted mitochondrial dynamics, and decreased mtDNA copy number, leading to impaired renal recovery.^[276] Therapeutic strategies targeting MQC include modulation of mitochondrial proteases such as LONP1, which maintain mitochondrial proteostasis and bioenergetics under stress, and have shown promise in mitigating renal injury.^[277,278] Stem cell-derived exosomes carrying microRNAs (e.g., miR-874-3p) can regulate necroptosis and mitochondrial fission via DRP1 dephosphorylation, promoting tubular epithelial cell repair after injury.^[279] Furthermore, pharmacological agents such as zileuton attenuate rhabdomyolysis-induced AKI by modulating mitochondrial dynamics and suppressing myeloid-derived suppressor cell-mediated inflammation.^[280] Recent studies have shown that mtDNA, as a key molecule linking mitochondrial damage to sterile inflammation, plays a critical role in the pathogenesis of various kidney diseases.^[281] The age-dependent accumulation of mt-tRNA mutations in mouse kidneys is closely associated with mitochondrial nephropathy.^[282] Targeted regulation of mitochondrial RNA by Mito-tempo may alleviate kidney pathology.^[283,284]

In summary, MQC mechanisms encompassing mitochondrial dynamics, mitophagy, biogenesis, and proteostasis are integral to kidney health and disease.^[115] Disruptions in these processes underlie the pathogenesis of both acute and chronic kidney diseases, including AKI, CKD, and DKD. Therapeutic interventions aimed at restoring mitochondrial homeostasis and quality control hold significant promise for the complexity of MQC regulation, cell type-specific effects, and potential adverse effects. Future research should focus on elucidating precise molecular pathways, developing targeted therapeutics, and identifying biomarkers to monitor mitochondrial health during kidney injury and repair.^[98,285,286]

MQC and metabolic diseases

MQC plays a pivotal role in the pathogenesis and progression of metabolic diseases, which encompass a spectrum of disorders such as metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic syndrome, T2DM, diabetic cardiomyopathy, DKD, and polycystic ovary syndrome (PCOS). These diseases share a common thread of mitochondrial dysfunction characterized by impaired mitochondrial biogenesis, abnormal dynamics (fusion and fission), defective mitophagy, and disrupted proteostasis, leading to compromised energy metabolism, increased oxidative stress, and inflammation. MASLD, formerly known as non-alcoholic fatty liver disease, exemplifies the central role of MQC in metabolic disorders. In MASLD, dysfunctional mitochondria contribute to hepatic steatosis, inflammation, and fibrosis by failing to maintain energy homeostasis and by generating excessive ROS.^[287] Experimental models of MAFLD induced by high-fat diet demonstrate increased mitochondrial ROS production, mtDNA damage, reduced mitochondrial biogenesis, impaired fusion, and defective mitophagy, underscoring the failure of MQC as a core event in hepatic mitochondrial dysregulation.^[288] These mitochondrial perturbations not only exacerbate lipid accumulation but also activate inflammatory pathways, including the cyclinc GMP-AMP synthase–stimulator of interferon genes (cGAS–STING) axis, which further aggravate liver injury.^[289]

In diabetic cardiomyopathy, a major complication of diabetes, MQC dysfunction manifests as excessive mitochondrial fission, reduced fusion, and impaired mitophagy, resulting in the accumulation of fragmented and dysfunctional mitochondria within cardiomyocytes. This mitochondrial derangement promotes oxidative stress, metabolic reprogramming, and cell death, ultimately leading to cardiac dysfunction.^[290,291] Therapeutic agents such as sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists exert cardioprotective effects partly by restoring MQC balance.^[291] Similarly, DKD, the leading cause of end-stage renal disease, is characterized by mitochondrial dysfunction due to defective MQC mechanisms, including impaired mitochondrial dynamics, mitophagy, and biogenesis. These defects lead to the accumulation of damaged mitochondria, increased ROS production, and renal tissue injury.^[272,292] Natural products and pharmacological agents targeting MQC pathways show promise in ameliorating DKD by restoring mitochondrial homeostasis.^[293]

Mitochondrial dysfunction also underlies insulin resistance and metabolic syndrome, conditions marked by obesity, dyslipidemia, and hypertension. Impaired MQC contributes to oxidative stress and chronic low-grade inflammation, which are central to metabolic syndrome pathogenesis.^[294,295] For instance, the mitochondrial protease LONP1, a key player in mitochondrial proteostasis, emerges as a potential molecular target for metabolic syndrome therapy.^[295] In PCOS, mitochondrial abnormalities in granulosa cells, including decreased MMP, reduced ATP production, and increased ROS, are linked to impaired oocyte quality and reproductive dysfunction. Downregulation of SIRT3, a regulator of mitochondrial function and glucose metabolism, mediates these defects, highlighting the role of MQC in reproductive metabolic disorders.^[296,297]

Furthermore, mitochondrial stress responses such as the UPR^mt and mitochondrial proteases are integral to MQC and cellular adaptation in metabolic diseases. Their dysregulation exacerbates mitochondrial proteotoxicity, contributing to disease progression.^[298,299] Therapeutic strategies enhancing MQC, including nicotinamide adenine dinucleotide (NAD)+ boosters, have demonstrated efficacy in improving mitochondrial function and reducing metabolic dysfunction in diabetes and neurodegenerative disease models.^[300] Additionally, interventions such as photobiomodulation and natural compounds (e.g., asperuloside, bavachin) improve mitochondrial function and biogenesis, mitigating metabolic disease phenotypes.^[301–303]

In summary, MQC is a fundamental determinant of mitochondrial integrity and function in metabolic diseases. The intricate balance of mitochondrial biogenesis, dynamics, mitophagy, and proteostasis is essential for cellular energy homeostasis and prevention of oxidative damage. Disruption of these processes contributes to the pathogenesis of MASLD, diabetic complications, metabolic syndrome, and PCOS. Targeting MQC pathways offers promising therapeutic avenues to restore mitochondrial function, reduce oxidative stress, and improve metabolic outcomes. Ongoing research continues to elucidate the molecular mechanisms of MQC dysregulation and to develop mitochondria-targeted therapies that may transform the management of metabolic diseases.

MQC and tumors

MQC plays a pivotal role in tumor biology, influencing cancer development, progression, metastasis, and therapeutic responses through the maintenance of mitochondrial homeostasis. Tumor cells exhibit high metabolic demands and mitochondrial activity, which leads to increased production of mitochondrial ROS (mtROS), accumulation of mtDNA mutations, and mitochondrial dysfunction. To survive and proliferate under these conditions, cancer cells exploit MQC mechanisms, including mitochondrial dynamics (fusion and fission), mitophagy, mitochondrial biogenesis, UPR^mt, and MDVs, to preserve mitochondrial integrity and function.^{[233,304,305]} For example, the UPR^mt is activated in cancer cells to mitigate mitochondrial stress by promoting the refolding or degradation of damaged mitochondrial proteins, thereby supporting tumor growth and resistance to therapy.^[233,304] Similarly, mitochondrial dynamics regulated by proteins such as DRP1 are critical for tumor cell survival, proliferation, and metastasis, with DRP1-mediated mitochondrial fission linked to cancer stemness and chemoresistance.^[306,307]

In gastrointestinal tumors, disruptions in mitochondrial homeostasis, including altered mitochondrial biogenesis, dynamics, and mitophagy, contribute to tumorigenesis and progression, suggesting that targeting MQC pathways could offer therapeutic benefits.^[305] The p53/Mieap-regulated MQC pathway exemplifies the tumor-suppressive role of MQC, where Mieap induces mitochondrial repair or elimination of damaged mitochondria, and its inactivation via promoter methylation or p53 mutation is frequently observed in gastric and esophageal cancers, correlating with impaired mitochondrial apoptosis and tumor progression.^[308] Moreover, mitochondrial proteases such as ClPP maintain mitochondrial proteostasis, and their dysregulation is implicated in hematologic and solid tumors, highlighting ATP-dependent unfoldase ClpX (ClpXP) as a potential therapeutic target.^[309]

MDVs, selectively remove damaged mitochondrial components and have been shown to influence tumor progression and chemoresistance. In chemoresistant ovarian cancer cells, defective mitochondria–lysosome communication leads to increased MDVs secretion, which can transfer mitochondrial components to recipient cells, modulating mitochondrial function and promoting chemoresistance.^[310,311] Additionally, the regulation of mitochondrial plasticity by proteins such as complement C1q binding protein (C1QBP) affects tumor metastasis and immune responses, influencing the competitive balance between tumor and immune cells within the tumor microenvironment.^[312,313]

Metabolic reprogramming in tumors is closely linked to MQC. For instance, inhibition of pyruvate dehydrogenase kinase 1 (PDK1) shifts glucose metabolism from glycolysis to oxidative phosphorylation, but concurrently disrupts MQC by altering mitochondrial morphology and reducing mitophagy and biogenesis proteins, leading to increased mitochondrial stress and ROS production.^[248] Furthermore, mitochondrial dysfunction induced by targeted therapies or metabolic interventions, such as mitochondrial iron chelation or use of nanosystems inducing mitochondrial damage, has shown promise in suppressing tumor growth and metastasis by exploiting MQC pathways.^[314,315]

MQC also intersects with immune regulation in tumors. In hepatocellular carcinoma (HCC), mitochondrial dysfunction in T cells within the tumor microenvironment contributes to T-cell exhaustion, impairing antitumor immunity. Strategies combining immune checkpoint inhibitors with mitochondrial biogenesis modulation aim to restore T-cell function by enhancing MQC.^[316] Similarly, mitochondrial dysfunction and MQC dysregulation affect tumor-infiltrating lymphocytes in head and neck squamous cell carcinoma, influencing cytotoxic responses.^[317]

Therapeutically, targeting MQC offers multiple avenues. In triple-negative breast cancer (TNBC), abnormal MQC contributes to chemoresistance, immune evasion, metastasis, and cancer stemness, and interventions aimed at key MQC nodes provide potential for precision therapy.^[318] Drugs such as berberine and proguanil have been shown to induce mitochondrial dysfunction and apoptosis in tumor cells by modulating MQC pathways.^[319,320] Moreover, combining mitochondrial dysfunction-inducing agents with photodynamic therapy or chemotherapy enhances treatment efficacy and overcomes multidrug resistance by disrupting MQC.^[321,322]

In summary, MQC is intricately involved in tumor biology, affecting mitochondrial integrity, metabolic adaptation, immune interactions, and therapeutic resistance. The dual role of MQC in maintaining mitochondrial function to support tumor survival and as a potential vulnerability offers promising targets for cancer therapy. Advances in understanding the molecular mechanisms of MQC dysregulation in tumors, along with the development of agents modulating these pathways, could lead to novel and effective anticancer strategies.^{[233,323,324]} Mitochondrial dysfunction and diseases, related regulatory pathways, and intervention strategies are summarized in Table 1.

Table 1.

Mitochondrial dysfunction and diseases.

Diseases	Targets and pathways	Interventions
NDD	PINK1/PRKN,^[325] Drp1,^[326,327] PGC-1α^[328]	Mdivi-1,^[328,329] Resveratrol analogues,^[330] P110,^[326] Q10,^[331] idebenone,^[332] Urolithin A,^[333] Mfn2 agonist^[334]
CVD	mPTP,^[335] Drp1,^[336] FUNDC1,^[337] BNIP3^[338]	Cyclosporine A,^[339] Drp1 inhibitor,^[336] SUL-238^[340]
AKI, CKD	Drp1,^[341] PGC-1α,^[342] cardiolipin^[343]	Drp1 inhibitor,^[341] SS-31^[343]
Cancer	Mitophagy,^[344] BCL-2,^[345] OXPHOS^[346]	HCQ,^[347] venetoclax,^[348] IACS-010759,^[346] Mdivi-1^[349]
Metabolic disease	PGC-1α,^[350] AMPK,^[351] mitophagy^[352]	Exercise,^[350] calorie restriction,^[353] metformin,^[354] MOTS-c,^[355] urolithin A^[356]

Open in a new tab

AMPK: Adenosine monophosphate-activated protein kinase; AKI: Acute kidney injury; BCL-2: B-cell lymphoma 2; BNIP3: BCL2/adenovirus E1B 19 kDa protein-interacting protein 3; CKD: Chronic kidney disease; CVD: Cardiovascular disease; Drp1: Dynamin-related protein 1; FUNDC1: FUN14 domain-containing protein 1; mPTP: Mitochondrial permeability transition pore; NDD: Neurodegenerative diseases; OXPHOS: Oxidative phosphorylation; PGC-1α: Peroxisome proliferator-activated receptor gamma coactivator 1-alpha; PINK1: PTEN-induced kinase 1; PRKN: Parkin.

Targeted MQC Therapeutic Strategies

Enhancing mitophagy

Enhancing mitophagy, the selective autophagic removal of damaged or dysfunctional mitochondria, has emerged as a critical therapeutic strategy in various pathological conditions characterized by mitochondrial dysfunction. In acquired cholesteatoma epithelial cells, mitophagy is notably enhanced, as evidenced by increased expression of autophagy markers LC3-II and mitophagy proteins BNIP3, PRKN, and PINK1, alongside elevated autophagic activity and autophagosome formation, suggesting a potential role of mitophagy in disease pathogenesis.^[357] Similarly, in neurodegenerative diseases such as AD, impaired mitophagy contributes to the accumulation of defective mitochondria, exacerbating neuronal damage. Pharmacological induction of mitophagy via enhancers such as urolithin A, NAD+, and resveratrol has shown promise in suppressing mutant amyloid precursor protein (APP)/beta-amyloid (Aβ) and Tau-induced mitochondrial and synaptic dysfunctions, highlighting mitophagy activation as a therapeutic target.^[358,359] In osteoarthritis, stabilization of hypoxia-inducible factor-1αpromotes mitophagy, alleviating cartilage degradation by mitigating apoptosis and senescence in chondrocytes under hypoxic conditions, indicating that enhancing mitophagy can protect joint tissues.^[360] Moreover, bronchial fibroblasts from severe asthmatic patients exhibit enhanced Pink/PRKN-mediated mitophagy, which contributes to fibroblast persistence and fibrosis, suggesting that modulating mitophagy flux could influence disease progression.^[361] Cardioprotective effects of agents such as canagliflozin in diabetic cardiomyopathy are partly mediated by activation of PINK1-PRKN-dependent mitophagy, which improves mitochondrial function and energy metabolism, underscoring the importance of mitophagy enhancement in cardiac diseases.^[362] Molecular regulators such as arrestin-3 and Mdm2 have been identified to bind and enhance PRKN activity, facilitating mitophagy and offering novel avenues for therapeutic intervention, especially in PD.^[363,364] Nutritional compounds prevalent in Mediterranean and Okinawan diets, including resveratrol, curcumin, and spermidine, also act as mitophagy enhancers, promoting brain health and potentially delaying neurodegeneration by maintaining mitochondrial quality.^[365] In neurodegenerative models, inhibition of nuclear receptor NR1D1 enhances autophagy and mitophagy, improving neuronal function and cognitive outcomes, thereby reinforcing the therapeutic potential of mitophagy activation.^[366] Experimental evidence from prion-infected cells and animal models demonstrates upregulated PINK1/PRKN-dependent mitophagy as a cellular response to mitochondrial damage, suggesting that enhancing this pathway may mitigate neurodegeneration.^[367] Natural compounds such as icaritin induce mitophagy via PINK1/PRKN signaling in HCC cells, and mitophagy inhibition enhances their anticancer efficacy, indicating that fine-tuning mitophagy can modulate therapeutic responses.^[368] In the context of sepsis-induced myocardial dysfunction, pharmacological agents such as Baricitinib enhance PINK1-PRKN-mediated mitophagy via inhibition of the Janus kinase 2 (JAK2)-AKT-mTOR pathway, reducing apoptosis and restoring energy metabolism, highlighting mitophagy enhancement as a cardioprotective mechanism.^[369] Furthermore, long non-coding RNAs (lncRNAs) such as rhabdomyosarcoma 2 associated transcript (RMST) have been shown to suppress mitophagy through post-translational modifications, suggesting that targeting lncRNAs could modulate mitophagy in gliomas.^[370] Coenzyme Q10 (CoQ10) protects against acetaminophen-induced liver injury by promoting mitophagy, emphasizing the role of mitophagy enhancers in drug-induced organ toxicities.^[371] Collectively, these studies underscore that enhancing mitophagy through genetic, pharmacological, or nutritional means can restore mitochondrial homeostasis, reduce oxidative stress, and improve cellular function across a spectrum of diseases. The PINK1–PRKN pathway remains a central axis in mitophagy regulation, and its modulation offers promising therapeutic avenues. However, the context-dependent effects of mitophagy, including its role in fibrosis or cancer cell survival, necessitate precise modulation strategies. Advances in understanding mitophagy mechanisms and the development of mitophagy-specific activators or inhibitors will be critical for translating these findings into clinical therapies for mitochondrial-related diseases.

Inhibition of excessive mitochondrial fission

Excessive mitochondrial fission, predominantly mediated by DRP1 and its interaction with adaptor proteins such as Fis1, Mff, MiD49, and MiD51, is a critical pathological hallmark in various diseases, including cardiovascular, neurodegenerative, metabolic, and inflammatory disorders. Under physiological conditions, mitochondrial fission and fusion are tightly balanced to maintain mitochondrial morphology, distribution, and function, which are essential for cellular homeostasis. However, pathological stimuli often trigger aberrant activation of DRP1, leading to excessive mitochondrial fragmentation, mitochondrial dysfunction, increased ROS production, impaired mitophagy, and ultimately cell death or dysfunction. Inhibiting this excessive fission has emerged as a promising therapeutic strategy to restore MQC and improve disease outcomes.

In obesity cardiomyopathy (OCM), lipotoxic stress induced by palmitate leads to excessive mitochondrial fission via DRP1/Fis1 interaction, resulting in mitochondrial dysfunction, increased oxidative stress, and release of extracellular mitochondria (exMito) that propagate inflammation and cardiac remodeling. The peptide inhibitor P110, which selectively disrupts DRP1/Fis1 interaction, effectively attenuates mitochondrial fragmentation, reduces exMito release, and ameliorates inflammation and contractile dysfunction in both in vitro and in vivo OCM models.^[372] Similarly, in diabetic cardiomyopathy, abnormal MQC characterized by excessive fission and insufficient fusion contributes to cardiomyocyte injury. Pharmacological agents targeting mitochondrial dynamics, including inhibition of DRP1-mediated fission, have shown cardioprotective effects by restoring mitochondrial morphology and function.^[291,373]

In vascular diseases such as atherosclerosis and vascular senescence, excessive mitochondrial fission mediated by DRP1 activation exacerbates mitochondrial dysfunction and oxidative stress. Inhibition of DRP1 with mdivi-1 or blockade of upstream signaling pathways (e.g., AT1R-Raf/MEK/ERK axis) attenuates mitochondrial fragmentation, enhances mitophagy, and reduces vascular inflammation and senescence.^[108,374] In neurodegenerative diseases, DRP1 hyperactivation induces pathological mitochondrial fragmentation, contributing to neuronal death. Rho-associated coiled-coil containing kinase 1 (ROCK1) kinase phosphorylates DRP1, promoting excessive fission and impairing mitophagy, while ROCK inhibition restores mitochondrial dynamics and confers neuroprotection in models of PD, AD, and ALS.^[63,375,376]

Mitochondrial fission also plays a pivotal role in IRI and neuroinflammation. In myocardial IRI, DRP1-mediated fission leads to mitochondrial fragmentation and cardiomyocyte apoptosis, which can be mitigated by DRP1 inhibitors that promote mitochondrial biogenesis through PGC-1α activation.^{[328,377,378]} In postoperative cognitive dysfunction (POCD), DRP1 inhibition reduces microglial activation, ROS production, and synaptic loss, improving cognitive outcomes.^[379] Moreover, in spinal cord injury, MSC-mediated mitochondrial transfer restores mitochondrial fusion and inhibits DRP1-dependent fission, thereby reducing neuronal ferroptosis.^[380]

Pharmacological agents such as mdivi-1, P110, and natural compounds have demonstrated efficacy in inhibiting DRP1-dependent mitochondrial fission, preserving mitochondrial function, and attenuating disease progression across multiple organ systems.^[380–382] Exercise interventions also modulate DRP1 activity, reducing excessive fission and improving mitochondrial and cellular metabolism in chronic diseases.^[383–385] Furthermore, traditional Chinese medicines like Zishen Tongyang Huoxue decoction (TYHX) regulate MQC by inhibiting DRP1 translocation and excessive fission through signaling axes involving VDAC1 and β-tubulin, offering additional therapeutic avenues.^[374]

Mechanistically, post-translational modifications of DRP1, including phosphorylation at Ser616 enhance its recruitment to mitochondria and fission activity, while inhibition of these modifications or blocking DRP1 assembly reduces pathological fission.^[386–388] Targeting upstream regulators such as nuclear receptor subfamily 4 group A member 1 (NR4A1), methyltransferase-like 3 (METTL3), and ROCK1, which modulate DRP1 activity and mitochondrial dynamics, also represents a promising strategy to curb excessive mitochondrial fission and its deleterious consequences.^[389–391]

In summary, inhibition of excessive mitochondrial fission by targeting DRP1 and its regulatory network is a critical component of MQC restoration. This approach holds significant therapeutic potential for a broad spectrum of diseases characterized by mitochondrial dysfunction, including cardiovascular diseases, neurodegenerative disorders, metabolic syndromes, and inflammatory conditions. Ongoing research into specific inhibitors, signaling pathways, and combinatorial therapies will further refine strategies to suppress pathological mitochondrial fission while preserving physiological mitochondrial dynamics essential for cellular health.

MQC as a novel therapeutic target: Future research directions and clinical applications

MQC has emerged as a pivotal therapeutic target across a spectrum of diseases, reflecting its fundamental role in maintaining cellular homeostasis and organ function. Dysfunctional MQC mechanisms—including impaired mitophagy, disrupted mitochondrial dynamics (fusion/fission), defective mitochondrial biogenesis, and compromised protein quality control—are implicated in the pathogenesis of neurodegenerative disorders, cardiovascular diseases, metabolic syndromes, cancers, and inflammatory conditions. The translational potential of targeting MQC lies in its ability to restore mitochondrial integrity, reduce oxidative stress, and modulate cell death pathways, thereby ameliorating disease progression and improving clinical outcomes.

In neurodegenerative diseases such as PD, AD, and HD, defective MQC leads to the accumulation of damaged mitochondria, increased ROS, and impaired bioenergetics, which exacerbate neuronal loss and cognitive decline. Pharmacological strategies that enhance mitophagy, modulate mitochondrial dynamics, or promote mitochondrial biogenesis have shown promise in preclinical models, suggesting avenues for disease-modifying therapies.^{[225,232,392]} For example, interventions such as intermittent fasting combined with exercise can augment NADPH levels and mitophagy, thereby protecting neurons from oxidative and proteotoxic stress in PD.^[393] Moreover, mitochondrial proteases and chaperones are being explored as druggable targets in cancer therapy, with modulators of ClPP and LonP1 proteases undergoing clinical evaluation.^[394]

Cardiovascular diseases, including diabetic cardiomyopathy and anthracycline-induced cardiotoxicity, also exhibit MQC impairment characterized by mitochondrial fragmentation, defective mitophagy, and reduced biogenesis. Therapeutic agents targeting these pathways, such as Sirtuin activators and natural compounds, have demonstrated cardioprotective effects by preserving mitochondrial function and reducing oxidative damage.^{[291,395,396]} Similarly, in IRI and heart failure, restoring MQC balance through modulation of mitochondrial dynamics and autophagy represents a promising strategy to limit myocardial damage.^[243,397]

In metabolic diseases and organ-specific pathologies, MQC-targeted therapies are gaining traction. For instance, in osteoarthritis and osteoporosis, mitochondrial dysfunction in chondrocytes and bone cells contributes to disease progression; agents that enhance mitochondrial biogenesis and mitophagy, such as Sirtuin activators, show potential to restore tissue homeostasis and function.^[398,399] In pulmonary diseases such as chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis, targeting molecules involved in mitochondrial dynamics (e.g., PINK1, DRP1) may mitigate oxidative stress and cellular senescence, although the complexity of mitochondrial autophagy roles necessitates further investigation.^[400,401] Moreover, MQC modulation holds promise in kidney diseases, including acute and diabetic kidney injury, where maintaining mitochondrial homeostasis can prevent cell death and fibrosis.^[292,402]

Recent advances highlight innovative therapeutic modalities such as mitochondrial transplantation, mitochondrial-targeted antioxidants, nanozyme-based delivery systems, and MitoEVs that facilitate intercellular mitochondrial transfer and quality control, opening new frontiers for clinical application.^[147,403] Epigenetic regulation of MQC components, including DNA methylation and non-coding RNAs, also represents an emerging area for therapeutic intervention, particularly in liver fibrosis and cancer.^[404,405]

Despite these advances, several challenges impede clinical translation. These include the heterogeneity of mitochondrial dysfunction across diseases and patients, off-target effects of MQC modulators, limited specificity of delivery systems, and the need for reliable biomarkers to monitor mitochondrial health and therapeutic efficacy. Future research should prioritize the development of personalized MQC-based therapies guided by biomarker profiling, refinement of targeted delivery technologies, and comprehensive evaluation of long-term safety and effectiveness in clinical trials.

In conclusion, MQC represents a versatile and compelling target for therapeutic development across diverse diseases. Continued elucidation of MQC molecular mechanisms, coupled with innovative drug design and delivery approaches, holds the promise of transforming disease management and improving patient outcomes in the coming years.^{[151,186,406]}

Emerging Therapies Targeting Mitochondrial Dysfunction

Small molecule drugs

Small molecule drugs have emerged as promising agents for modulating MQC mechanisms, offering therapeutic potential across a broad spectrum of diseases characterized by mitochondrial dysfunction. These compounds can target key mitochondrial processes such as dynamics (fusion and fission), mitophagy, biogenesis, and proteostasis, thereby restoring mitochondrial homeostasis and cellular health. For instance, natural small molecules such as notoginsenoside R1 (NGR1) have demonstrated efficacy in sepsis models by targeting DRP1-mediated mitochondrial fission, preventing mitochondrial fragmentation, and improving organ function and survival outcomes.^[407] Similarly, caffeine at low doses alleviates high-altitude pulmonary edema by promoting PINK1/PRKN-dependent mitophagy and mitochondrial fission, highlighting its role in maintaining mitochondrial quality under hypoxic stress.^[408] In the context of infectious diseases, small molecules such as MLN8054, an Aurora kinase A inhibitor, have been identified through organoid-based drug screening to reverse Helicobacter pylori VacA-induced mitochondrial damage in gastric pit cells, underscoring the utility of small molecules in mitigating pathogen-induced mitochondrial dysfunction.^[409]

Beyond natural compounds, synthetic small molecules have also been developed to directly modulate MQC pathways. Niclosamide, a PINK1 activator, mitigates paclitaxel-induced peripheral neuropathy by restoring mitochondrial homeostasis and suppressing mitochondrial ROS and aberrant mitophagy in neuronal models.^[410] Targeting mitochondrial proteostasis, small molecules such as ONC201 hyperactivate ClpP protease, disrupting mitochondrial protein quality control and offering potential therapeutic avenues in cancer.^[411] In neurodegenerative diseases, UMI-77, a BH3-mimetic, induces mitophagy by enhancing MCL1’s interaction with LC3A, thereby improving cognitive function in AD models.^[412] Similarly, small molecule modulators of mitophagy are being systematically characterized to ensure methodological rigor and therapeutic efficacy, as highlighted in comprehensive reviews that propose frameworks for evaluating such compounds.^[413]

Small molecules also exert protective effects in metabolic and cardiovascular diseases by modulating mitochondrial dynamics and bioenergetics. KU-596, improves mitochondrial bioenergetics and reduces mitophagy in diabetic sensory neurons via heat shock protein 70 (Hsp70)-dependent mechanisms.^[414] Pharmacological agents such as metformin and resveratrol enhance mitochondrial biogenesis through activation of PGC-1α, AMPK, and SIRT1 pathways, offering metabolic benefits.^[415] In cardiovascular contexts, compounds targeting mitochondrial dynamics and metabolism in macrophages modulate inflammatory responses and cell death, thereby influencing disease progression.^[416] Traditional Chinese medicine formulations such as Linggui Zhugan decoction have been shown to ameliorate doxorubicin-induced cardiotoxicity by preserving mitochondrial structure and function through the AMPK-FOXO3a-B cell translocation gene (BTG2) axis.^[417]

In oncology, small-molecule drugs targeting mitochondrial dynamics and function present innovative therapeutic strategies. For example, methiothepin, a serotonin receptor antagonist, suppresses tumor growth in placental choriocarcinoma by attenuating mitochondrial function and inducing metabolic shifts.^[418] Benzothiophene derivatives identified via high-content screening enhance basal mitophagy, improving mitochondrial function and insulin secretion in beta cells.^[419] Small molecules that activate mitochondrial fusion or inhibit fission, such as novel isoxazole derivatives and indomethacin-based compounds, restore mitochondrial morphology and induce apoptosis in HD and various cancer cell models.^[420,421] Additionally, small molecule inhibitors of deubiquitinases such as ubiquitin-specific protease 30 (USP30) modulate mitophagy pathways and are being explored for neurodegenerative diseases.^[422]

Emerging approaches also involve small molecules that modulate mitochondrial electron flow and redox status, providing novel means to assess and restore mitochondrial quality.^[423] Fluorescent small molecule probes conjugated with mitochondria-targeting moieties enable imaging and photodynamic therapy, exemplified by NIR-II fluorophores and aggregation-induced emission (AIE) probes that combine diagnostic and therapeutic functions.^[424,425] Furthermore, small molecules that regulate mitochondrial calcium channels and lysosomal function, such as transient receptor potential mucolipin 1 (TRPML1) agonists, mitigate mitochondrial damage and oxidative stress, highlighting the interconnectedness of mitochondrial and lysosomal quality control.^[426]

Collectively, these studies illustrate the diverse chemical space of small-molecule drugs capable of targeting MQC mechanisms. Their ability to modulate mitochondrial dynamics, mitophagy, biogenesis, proteostasis, and bioenergetics positions them as versatile tools for treating diseases ranging from neurodegeneration and metabolic disorders to cancer and infectious diseases. Ongoing efforts to optimize their specificity, efficacy, and delivery, including the use of organoid models and structure-based drug design, are critical for translating these promising agents into clinical therapies.^[151]

Gene therapy

Gene therapy has emerged as a promising and innovative approach for treating mitochondrial diseases and dysfunctions by directly targeting the underlying genetic defects within mtDNA or nuclear-encoded mitochondrial genes. Unlike traditional symptomatic management, gene therapy aims to correct or compensate for the defective genes responsible for mitochondrial dysfunction, thereby restoring mitochondrial integrity and function. Advances in molecular biology and gene editing technologies, such as clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9), transcription activator-like effector nucleases (TALENs), zinc finger nucleases, and base editors, have facilitated the development of strategies to manipulate mitochondrial genomes or nuclear genes encoding mitochondrial proteins with increasing precision and efficacy.^[427–431] These approaches include mitochondrial gene replacement, allotopic expression (nuclear expression of mitochondrial genes with mitochondrial targeting sequences), mitochondrial genome editing, and mitochondrial RNA interference.

A critical challenge in mitochondrial gene therapy is the unique biology of mitochondria, including their double-membrane structure, polyploidy of mtDNA, heteroplasmy (coexistence of mutant and wild-type mtDNA), and limited DNA repair mechanisms. These factors complicate the delivery and editing of mitochondrial genes compared to nuclear genes.^[432,433] To overcome these hurdles, novel delivery systems such as adeno-associated virus (AAV) vectors, lipid nanoparticles, and mitochondria-targeted nanocarriers have been developed to facilitate efficient and targeted transduction of mitochondrial or nuclear genes influencing mitochondrial function.^{[52,434–436]}

Several preclinical and clinical studies have demonstrated the therapeutic potential of gene therapy in various mitochondrial diseases. For instance, AAV9-mediated gene therapy delivering functional copies of mitochondrial genes such as deoxyguanosine kinase (DGUOK) and NADH:ubiquinone oxidoreductase subunit S6 (NDUFS6) has shown efficacy in preventing or ameliorating mitochondrial hepatocerebral DNA depletion syndrome and mitochondrial cardiomyopathy, respectively, in mouse models.^[434,437] In neurodegenerative diseases such as PD and AD, gene therapy strategies targeting mitochondrial complex I dysfunction via allotopic expression of yeast NDI1 or other mitochondrial genes have improved mitochondrial function and reduced neuropathological features in cell and animal models.^[438,439] Similarly, gene editing of the SMN1 gene in spinal muscular atrophy models has shown promise in restoring mitochondrial function in skeletal muscle.^[440]

In addition to monogenic mitochondrial diseases, gene therapy is being explored for complex disorders where mitochondrial dysfunction plays a pivotal role, such as sarcopenia, cardiac hypertrophy, and metabolic syndromes. For example, gene therapy targeting MQC protein such as oligomycin sensitivity conferring protein (OSCP) has demonstrated protective effects against cardiac hypertrophy by improving mitochondrial respiration and reducing oxidative stress.^[433] Moreover, gene therapies modulating mitochondrial dynamics and biogenesis through pathways involving RAB5A, member RAS oncogene family (Rab5a)/mTOR have shown potential in ameliorating sarcopenia associated with T2DM.^[441]

The development of mitochondrial gene editing tools has advanced significantly, with the emergence of base editing technologies capable of precise mtDNA modifications without inducing double-strand breaks, thereby minimizing off-target effects and genomic instability.^[431,442] However, efficient delivery of gene editing components into mitochondria remains a major obstacle, necessitating further research into mitochondrial import mechanisms and vector optimization.^[429,432]

Clinical translation of mitochondrial gene therapy faces challenges, including heterogeneity of mitochondrial diseases, tissue-specific delivery, immune responses to vectors, and long-term safety concerns. Nonetheless, ongoing clinical trials, particularly for Leber hereditary optic neuropathy (LHON), exemplify the progress toward effective gene-based treatments.^[427,443] Additionally, gene therapy approaches are being combined with other modalities such as mitochondrial transplantation, antioxidant therapy, and metabolic interventions to enhance therapeutic outcomes.^[52,444]

In summary, gene therapy targeting mitochondrial dysfunction represents a rapidly evolving field with significant therapeutic potential. Advances in gene delivery systems, genome editing technologies, and understanding of mitochondrial biology are paving the way for personalized and effective treatments for mitochondrial diseases and related disorders. Continued research is essential to overcome current limitations and translate these promising strategies into clinical practice to improve patient outcomes.^{[427,428,432,443]}

Nutritional interventions

Nutritional interventions have emerged as a pivotal strategy for modulating MQC and improving health outcomes in various diseases, particularly those associated with aging, metabolic dysfunction, and muscle degeneration. A growing body of evidence underscores the role of specific nutrients, dietary patterns, and bioactive compounds in enhancing mitochondrial biogenesis, dynamics, mitophagy, and oxidative phosphorylation, thereby preserving mitochondrial function and cellular homeostasis. Medium-chain fatty acids (MCFAs), especially caprylic acid (C8), have been demonstrated to promote mitophagy via the PINK1–PRKN pathway, enhance oxidative phosphorylation, reduce mitochondrial oxidative stress, and facilitate skeletal muscle differentiation and maturation, suggesting their therapeutic potential in sarcopenia management.^[445] Similarly, omega-3 polyunsaturated fatty acids (PUFAs) have been linked to improved muscle membrane composition and function, attenuation of pro-inflammatory oxidative stress, and activation of mitochondrial signaling pathways, which collectively support physical performance across the lifespan.^[446] Dietary antioxidants such as chlorogenic acid and resveratrol have shown efficacy in ameliorating high-fat diet-induced mitochondrial dysfunction and oxidative stress in skeletal muscle and intestinal tissues, respectively, by promoting mitochondrial biogenesis and enhancing antioxidant defenses.^[447,448] Moreover, multi-ingredient nutritional supplements containing compounds such as α-lipoic acid, CoQ10, and green tea extract have been associated with improved mitochondrial function, weight loss, and metabolic health in overweight and obese individuals, highlighting the translational relevance of mitochondrial-targeted nutrition.^[449]

Dietary patterns such as the Mediterranean diet and ketogenic diet exert beneficial effects on mitochondrial health by modulating oxidative phosphorylation, mitochondrial dynamics, and mitophagy, which are critical in the prevention and management of metabolic diseases including non-alcoholic fatty liver disease (NAFLD) and MASLD.^[450,451] Ketogenic diets have demonstrated cardioprotective effects in diabetic models by balancing mitochondrial dynamics and inhibiting apoptosis through the PI3K/AKT pathway, further emphasizing the role of nutritional ketosis in mitochondrial preservation.^[452] Time-restricted eating, a form of intermittent fasting, has been shown to improve mitochondrial function and quality of life in patients with postural orthostatic tachycardia syndrome, suggesting that meal timing and caloric restriction can positively influence mitochondrial bioenergetics.^[453] Caloric restriction itself remains a cornerstone intervention that enhances mitochondrial biogenesis and function, partly through upregulation of PGC-1α, a master regulator of mitochondrial metabolism, thereby contributing to longevity and reduced incidence of age-related diseases.^[454,455]

Micronutrients and bioactive compounds such as vitamin D, minerals, polyphenols, and urolithin A have demonstrated modulatory effects on mitochondrial function and oxidative stress, which translate into improved muscle health, reduced inflammation, and enhanced metabolic resilience.^[456–459] For instance, urolithin A, a gut microbiome-derived metabolite, activates mitophagy and MQC pathways, resulting in improved muscle function during aging and reduced cardiovascular risk markers in humans.^[459,460] The interplay between diet, microbiome, and mitochondria is increasingly recognized as a critical axis influencing systemic health, with dietary fibers and fermented foods modulating gut microbial composition and mitochondrial function synergistically.^[461,462]

In pathological contexts such as obesity, high-fat diets induce mitochondrial dysfunction, oxidative stress, and inflammation, contributing to skeletal muscle and renal injury. Nutritional interventions targeting mitochondrial health, including antioxidant supplementation and modulation of lipid metabolism, have shown promise in mitigating these adverse effects.^{[458,463,464]} Furthermore, specific dietary components such as manganese at tolerable upper intake levels, can activate mitophagy and restore mitochondrial function in neurodegenerative disease models, exemplifying the therapeutic potential of micronutrient optimization.^[465]

Emerging nutritional strategies also encompass the use of nanotechnology to enhance the bioavailability and efficacy of mitochondrial-targeted compounds, as demonstrated in animal studies with resveratrol-loaded nanoparticles and other nutraceutical nanocompounds, which improve antioxidant capacity, mitochondrial function, and exercise performance.^[466] Additionally, dietary interventions have been explored in clinical settings for neurological disorders such as migraine and neurodegeneration, where co-supplementation with alpha-linolenic acid and L-carnitine or antioxidant-rich diets have shown potential benefits mediated through mitochondrial protection and anti-inflammatory effects.^[462,467]

Collectively, these findings highlight those nutritional interventions, ranging from specific fatty acids and vitamins to comprehensive dietary patterns and supplementation strategies, play a crucial role in maintaining MQC and function. Such interventions offer promising avenues for the prevention and management of age-related sarcopenia, metabolic diseases, neurodegenerative disorders, and cardiovascular conditions. Future research should aim to elucidate optimal nutrient combinations, dosing regimens, and personalized approaches integrating genetic and microbiome profiles to maximize mitochondrial health and overall clinical outcomes.

Mitochondrial transplantation

Mitochondrial transplantation involves the delivery of healthy, functional mitochondria into damaged or dysfunctional cells, aiming to restore cellular energy metabolism and improve cell viability. Mitochondrial transplantation technology (MTT) involves the isolation of healthy, functional mitochondria from donor cells or tissues and their subsequent delivery into recipient cells or tissues harboring dysfunctional mitochondria. This process aims to replenish or replace defective mitochondria, thereby restoring bioenergetic capacity and ameliorating cellular and tissue dysfunction.^[468,469] The concept of mitochondrial transplantation is inspired by the natural intercellular mitochondrial transfer phenomena observed in physiological and pathological contexts. Cells can exchange mitochondria through tunneling nanotubes, VEs, or direct uptake mechanisms, facilitating the rescue of damaged cells by restoring mitochondrial function.^[470,471] Harnessing this intrinsic cellular capability, exogenous mitochondrial transplantation seeks to augment or substitute defective mitochondria in target tissues. Preclinical studies have demonstrated the feasibility and therapeutic benefits of MTT in diverse disease models, including IRI of the heart, neurodegenerative diseases, acute lung injury, and metabolic disorders.^[472–475] Encouragingly, early-phase clinical trials, particularly in cardiac IRI, have shown safety and potential efficacy, marking a critical milestone towards clinical translation.^[476,477] Furthermore, techniques such as mitochondrial base editing using double-stranded DNA deaminase toxin A-derived cytosine base editor (DdCBE) or CRISPR-based approaches enable correction of pathogenic mtDNA mutations or enhancement of mitochondrial bioenergetics in donor mitochondria, advanced MTT in autologous mitochondrial modification and transplantation.^[478,479]

Despite these promising advances, several challenges remain before mitochondrial transplantation can be widely adopted in clinical practice. Key issues include optimizing mitochondrial isolation techniques to ensure viability and functionality, determining the most effective delivery routes and dosages, and understanding the mechanisms governing mitochondrial internalization and integration into host cells.^[480,481] Moreover, the immunogenicity of transplanted mitochondria, especially in allogeneic settings, and the stability of mitochondria in extracellular environments rich in calcium ions pose significant hurdles.^[469,482] Advances in engineered mitochondria and synthetic biology approaches offer potential solutions to enhance mitochondrial stability, targeting, and therapeutic efficacy.^[483] Additionally, the development of biomaterials and delivery systems to facilitate mitochondrial uptake and retention in target tissues is an active area of research.^[484] The optimization and innovation in mitochondrial transplantation encompass the integration of biomaterials, nanotechnology, gene editing, and multimodal therapies. These strategies enhance mitochondrial viability, targeting, and therapeutic potential, paving the way for effective clinical applications across a spectrum of mitochondrial-related diseases.

Conclusions and Future Directions

MQC stands as a cornerstone in maintaining cellular health and preventing a broad spectrum of diseases. From an expert perspective, the evolution of research in this field has illuminated the intricate mechanisms by which cells monitor and preserve mitochondrial integrity, including processes such as mitophagy, mitochondrial biogenesis, and dynamics such as fission and fusion. These mechanisms collectively ensure the removal of damaged mitochondria and the replenishment of functional ones, thereby sustaining cellular energy homeostasis and reducing oxidative stress.

Balancing the diverse research perspectives reveals a complex but coherent picture: while some studies emphasize the pivotal role of mitophagy in neurodegenerative diseases, others highlight mitochondrial biogenesis as a therapeutic target in metabolic disorders. This diversity underscores the necessity of an integrated approach that considers the multifaceted nature of MQC pathways and their tissue-specific roles. For instance, in neurodegenerative diseases such as PD and AD, impaired mitophagy leads to the accumulation of dysfunctional mitochondria, contributing to neuronal death. Conversely, in metabolic syndromes and cardiovascular diseases, dysregulated mitochondrial dynamics and biogenesis disrupt energy metabolism and promote pathological remodeling.

The impact of these findings extends beyond basic science, offering promising avenues for therapeutic intervention. Targeting MQC mechanisms holds potential for the development of novel treatments aimed at restoring mitochondrial function. Pharmacological agents that enhance mitophagy or stimulate mitochondrial biogenesis could mitigate disease progression by reinstating cellular homeostasis. Moreover, advances in gene editing and molecular biology provide tools to modulate specific components of MQC pathways, paving the way for personalized medicine approaches.

However, the translation of these insights into clinical practice demands careful consideration of the balance between mitochondrial turnover and cellular demands. Excessive activation of mitophagy, for example, may lead to unintended depletion of mitochondria, whereas insufficient clearance allows accumulation of damaged organelles. Therefore, future research must strive to delineate the optimal modulation of MQC tailored to distinct pathological contexts.

Looking ahead, the future of MQC research and its therapeutic translation hinges on several critical advancements. First, there is a pressing need to move beyond conventional small molecules and develop next-generation therapeutics, such as mitochondria- or MQC-component-specific PROTACs and degraders, to achieve precise and potent modulation of dysfunctional pathways with minimized off-target effects.^[485] Second, the development of advanced spatiotemporal biosensors for real-time, dynamic monitoring of MQC processes in vivo is essential to capture the nuanced and transient changes in mitochondrial health during disease progression and therapeutic intervention.^[485,486] Third, generating comprehensive, human tissue-specific multi-omics atlases (encompassing transcriptomic, proteomic, and lipidomic data) of MQC networks across the spectrum of health, aging, and various diseases will be invaluable for deciphering context-dependent regulatory logic and identifying novel, disease-specific nodal points for intervention.^[318,487] Fourth, the precise and context-dependent role of MDVs, a rapidly evolving MQC pathway, in different pathological settings—such as neurodegeneration or metabolic disease—requires systematic elucidation to harness its full diagnostic and therapeutic potential.^[233] Finally, integrating artificial intelligence and machine learning with the burgeoning multi-omics and clinical data holds transformative promise for accelerating the discovery of robust MQC-related biomarkers for early diagnosis and patient stratification, as well as for streamlining the identification and optimization of novel drug candidates.^[485] Addressing these interconnected frontiers will be pivotal in translating our mechanistic understanding of MQC into effective, personalized therapies for a wide array of human diseases.

In summary, the ongoing exploration of MQC mechanisms enriches our understanding of cellular physiology and disease etiology. By harmonizing diverse research findings and addressing the challenges of therapeutic targeting, the field is poised to contribute significantly to improving human health. Continued interdisciplinary efforts will be essential to harness the full potential of MQC-based strategies, ultimately transforming the management of metabolic, neurodegenerative, and cardiovascular diseases.

Funding

This work was supported by grants from the National Natural Science Foundation of China (NOs. 82370705, 82370730, and 82172502), Guangdong Provincial Key Laboratory of Autophagy and Major Chronic Non-Communicable Diseases (No. 2022B1212030003), the National Clinical Key Specialty Construction Project (Institute of Nephrology, Affiliated Hospital of Guangdong Medical University), and Special Project for Clinical and Basic Sci and Tech Innovation of Guangdong Medical University (No. GDMULCJC2024001).

Conflicts of interest

None.

Footnotes

How to cite this article: Liu ZZ, Hu WB, Sun L, Liu HF. Mitochondrial quality control in health and disease: Updates 2026. Chin Med J 2026;139:2851–2884. doi: 10.1097/CM9.0000000000004169

References

1.Schirrmacher V. Mitochondria at work: New Insights into regulation and dysregulation of cellular energy supply and metabolism. Biomedicines 2020;8:526. doi: 10.3390/biomedicines8110526. [DOI] [PMC free article] [PubMed] [Google Scholar]
2.Liu D Fan YB Tao XH Pan WL Wu YX Wang XH, et al. Mitochondrial quality control in sarcopenia: Updated overview of mechanisms and interventions. Aging Dis 2021;12:2016-2030. doi: 10.14336/AD.2021.0427. [DOI] [PMC free article] [PubMed] [Google Scholar]
3.Weber-Stiehl S, Jarke L, Castrillon-Betancur JC, Gilbert F, Sommer F. Mitochondrial function and microbial metabolites as central regulators of intestinal immune responses and cancer. Front Microbiol 2022;13:919424. doi: 10.3389/fmicb.2022.919424. [DOI] [PMC free article] [PubMed] [Google Scholar]
4.Li XD, Zuo SY, Xu LP, Song YP, Li W. Advances in macrophage metabolic reprogramming in hematological malignancies. Chin Med J BioMed 2025. doi: 10.65457/CMJBM-2025-0001. [Google Scholar]
5.Jadiya P, Tomar D. Mitochondrial protein quality control mechanisms. Genes (Basel) 2020;11:563. doi: 10.3390/genes11050563. [DOI] [PMC free article] [PubMed] [Google Scholar]
6.Tomar MS, Kumar A, Shrivastava A. Mitochondrial metabolism as a dynamic regulatory hub to malignant transformation and anti-cancer drug resistance. Biochem Biophys Res Commun 2024;694:149382. doi: 10.1016/j.bbrc.2023.149382. [DOI] [PubMed] [Google Scholar]
7.Santos EW, Khatoon S, Di Mise A, Zheng YM, Wang YX. Mitochondrial dynamics in pulmonary hypertension. Biomedicines 2023;12:53. doi: 10.3390/biomedicines12010053. [DOI] [PMC free article] [PubMed] [Google Scholar]
8.Li S Zhang J Liu C Wang Q Yan J Hui L, et al. The role of mitophagy in regulating cell death. Oxid Med Cell Longev 2021;2021:6617256. doi: 10.1155/2021/6617256. [DOI] [PMC free article] [PubMed] [Google Scholar]
9.Changaei M Azimzadeh Tabrizi Z Karimi M Kashfi SA Koochaki Chahardeh T Hashemi SM, et al. From powerhouse to modulator: Regulating immune system responses through intracellular mitochondrial transfer. Cell Commun Signal 2025;23:232. doi: 10.1186/s12964-025-02237-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
10.Chen Y Liu X Liu Y Li Y Li D Mei Z, et al. Mitochondrial quality control in diabetes mellitus and complications: Molecular mechanisms and therapeutic strategies. Cell Death Dis 2025;16:652. doi: 10.1038/s41419-025-07936-y. [DOI] [PMC free article] [PubMed] [Google Scholar]
11.Feng YF, Jin XR, Song JK, Hu J. Immunological tolerance and neurohomeostasis imbalance: Regulatory axis of neuropsychiatric diseases and new perspectives for intervention. Chin Med J BioMed. doi: 10.65457/CMJBM-2026-0001. [Google Scholar]
12.Wang Q, Yuan Y, Liu J, Li C, Jiang X. The role of mitochondria in aging, cell death, and tumor immunity. Front Immunol 2024;15:1520072. doi: 10.3389/fimmu.2024.1520072. [DOI] [PMC free article] [PubMed] [Google Scholar]
13.Eldeeb MA, Thomas RA, Ragheb MA, Fallahi A, Fon EA. Mitochondrial quality control in health and in Parkinson’s disease. Physiol Rev 2022;102:1721-1755. doi: 10.1152/physrev.00041.2021. [DOI] [PubMed] [Google Scholar]
14.Pal C. Targeting mitochondria with small molecules: A promising strategy for combating Parkinson’s disease. Mitochondrion 2024;79:101971. doi: 10.1016/j.mito.2024.101971. [DOI] [PubMed] [Google Scholar]
15.Cho SI Lee S Mok YG Lim K Lee J Lee JM, et al. Targeted A-to-G base editing in human mitochondrial DNA with programmable deaminases. Cell 2022;185:1764-1776.e12. doi: 10.1016/j.cell.2022.03.039. [DOI] [PubMed] [Google Scholar]
16.Mweene BC, Hatwiko H, Povia JP, Masenga SK. The role of mitochondrial dysfunction and dynamics in hypertensive heart disease: Mechanisms and recent advances. Biology (Basel) 2025;14:1212. doi: 10.3390/biology14091212. [DOI] [PMC free article] [PubMed] [Google Scholar]
17.Liu AM, Xu WL, Xiao H, Dong ED. Cardiac beta-adrenergic receptor regulation of mitochondrial function in heart failure (in Chinese). Acta Physiologica Sinica 2024;76:865-880. [PubMed] [Google Scholar]
18.Li Y Wang P Yang H He J Yang Y Tao Y, et al. In vivo identification of bioactive components of Poria cocos for adjusting mitochondria against metabolic dysfunction-associated fatty liver disease. Heliyon 2024;10:e35645. doi: 10.1016/j.heliyon.2024.e35645. [DOI] [PMC free article] [PubMed] [Google Scholar]
19.Cai Y Gan F Chen Y He Q Chen W Peng Z, et al. Mitochondria as a therapeutic target in metabolic disorders. Mini Rev Med Chem 2025. doi: 10.2174/0113895575403490250917111723. [DOI] [PubMed] [Google Scholar]
20.Wang SF, Tseng LM, Lee HC. Role of mitochondrial alterations in human cancer progression and cancer immunity. J Biomed Sci 2023;30:61. doi: 10.1186/s12929-023-00956-w. [DOI] [PMC free article] [PubMed] [Google Scholar]
21.Renaud CCN Trillet K Jardine J Merlet L Renoult O Laurent-Blond M, et al. The centrosomal protein 131 participates in the regulation of mitochondrial apoptosis. Commun Biol 2023;6:1271. doi: 10.1038/s42003-023-05676-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
22.Kuznetsov AV, Javadov S, Margreiter R, Hagenbuchner J, Ausserlechner MJ. Analysis of mitochondrial function, structure, and intracellular organization in situ in cardiomyocytes and skeletal muscles. Int J Mol Sci 2022;23:2252. doi: 10.3390/ijms23042252. [DOI] [PMC free article] [PubMed] [Google Scholar]
23.Fan H, Tan Y. Lipid droplet-mitochondria contacts in health and disease. Int J Mol Sci 2024;25:5878. doi: 10.3390/ijms25136878. [DOI] [PMC free article] [PubMed] [Google Scholar]
24.Stork BA, Dean A, York B. Methodology for measuring oxidative capacity of isolated peroxisomes in the Seahorse assay. J Biol Methods 2022;9: e160. doi: 10.14440/jbm.2022.374. [DOI] [PMC free article] [PubMed] [Google Scholar]
25.Joshi AS. Peroxisomal membrane contact sites in yeasts. Front Cell Dev Biol 2021;9:735031. doi: 10.3389/fcell.2021.735031. [DOI] [PMC free article] [PubMed] [Google Scholar]
26.Taghizadeh-Hesary F, Akbari H, Bahadori M, Behnam B. Targeted anti-mitochondrial therapy: The future of oncology. Genes (Basel) 2022;13:1728. doi: 10.3390/genes13101728. [DOI] [PMC free article] [PubMed] [Google Scholar]
27.Zhang X Zhang X Ren J Li J Wei X Yu Y, et al. Precise modelling of mitochondrial diseases using optimized mitoBEs. Nature 2025;639:735-745. doi: 10.1038/s41586-024-08469-8. [DOI] [PubMed] [Google Scholar]
28.Mi L Li YX Lv X Wan ZL Liu X Zhang K, et al. Computational design of a high-precision mitochondrial DNA cytosine base editor. Nat Struct Mol Biol 2025;32:2575-2586. doi: 10.1038/s41594-025-01714-2. [DOI] [PubMed] [Google Scholar]
29.Jia Y Han L Ramage CL Wang Z Weng CC Yang L, et al. Co-targeting BCL-XL and BCL-2 by PROTAC 753B eliminates leukemia cells and enhances efficacy of chemotherapy by targeting senescent cells. Haematologica 2023;108:2626-2638. doi: 10.3324/haematol.2022.281915. [DOI] [PMC free article] [PubMed] [Google Scholar]
30.DiGiovanni LF Khroud PK Carmichael RE Schrader TA Gill SK Germain K, et al. ROS transfer at peroxisome-mitochondria contact regulates mitochondrial redox. Science 2025;389:157-162. doi: 10.1126/science.adn2804. [DOI] [PubMed] [Google Scholar]
31.Koch C, Lenhard S, Raschle M, Prescianotto-Baschong C, Spang A, Herrmann JM. The ER-SURF pathway uses ER-mitochondria contact sites for protein targeting to mitochondria. EMBO Rep 2024;2:2071-2096. doi: 10.1038/s44319-024-00113-w. [DOI] [PMC free article] [PubMed] [Google Scholar]
32.Zhang H Yu X Ye J Li H Hu J Tan Y, et al. Systematic investigation of mitochondrial transfer between cancer cells and T cells at single-cell resolution. Cancer Cell 2023;41:1788-1802.e10. doi: 10.1016/j.ccell.2023.09.003. [DOI] [PMC free article] [PubMed] [Google Scholar]
33.Wang Y Yu HY Yi ZJ Qi LY Yang JS Xie HX, et al. Super mitochondria-enriched extracellular vesicles enable enhanced mitochondria transfer. Nat Commun 2025;16:9448. doi: 10.1038/s41467-025-64486-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
34.Popov LD. Mitochondrial biogenesis: An update. J Cell Mol Med 2020;24:4892-4899. doi: 10.1111/jcmm.15194. [DOI] [PMC free article] [PubMed] [Google Scholar]
35.Hood DA, Memme JM, Oliveira AN, Moradi N, Champsi S. Mitochondrial biogenesis in skeletal muscle. Adv Exp Med Biol 2025;1478:19-50. doi: 10.1007/978-3-031-88361-3_2. [DOI] [PubMed] [Google Scholar]
36.Horten P, Colina-Tenorio L, Rampelt H. Biogenesis of mitochondrial metabolite carriers. Biomolecules 2020;10:1008. doi: 10.3390/biom10071008. [DOI] [PMC free article] [PubMed] [Google Scholar]
37.Brischigliaro M, Sierra-Magro A, Ahn A, Barrientos A. Mitochondrial ribosome biogenesis and redox sensing. FEBS Open Bio 2024;14:1640-1655. doi: 10.1002/2211-5463.13844. [DOI] [PMC free article] [PubMed] [Google Scholar]
38.Cardanho-Ramos C, Morais VA. Mitochondrial biogenesis in neurons: How and where. Int J Mol Sci 2021;22:13059. doi: 10.3390/ijms222313059. [DOI] [PMC free article] [PubMed] [Google Scholar]
39.Chen D, Guo J, Li L. Catalpol promotes mitochondrial biogenesis in chondrocytes. Arch Physiol Biochem 2022;128:802-808. doi: 10.1080/13813455.2020.1727927. [DOI] [PubMed] [Google Scholar]
40.Ren P, Gong F, Chang L, Hong X, Xing L, Zhang H. Zafirlukast promotes mitochondrial respiration by stimulating mitochondrial biogenesis in human bronchial epithelial cells. J Mol Histol 2021;52:643-650. doi: 10.1007/s10735-021-09974-0. [DOI] [PubMed] [Google Scholar]
41.Kageyama M, Ito J, Shirasuna K, Kuwayama T, Iwata H. Mitochondrial reactive oxygen species regulate mitochondrial biogenesis in porcine embryos. J Reprod Dev 2021;67:141-147. doi: 10.1262/jrd.2020-111. [DOI] [PMC free article] [PubMed] [Google Scholar]
42.Liu L, Li Y, Chen G, Chen Q. Crosstalk between mitochondrial biogenesis and mitophagy to maintain mitochondrial homeostasis. J Biomed Sci 2023;30:86. doi: 10.1186/s12929-023-00975-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
43.Daskalaki I, Tavernarakis N. Mitochondrial biogenesis in organismal senescence and neurodegeneration. Mech Ageing Dev 2020;191:111345. doi: 10.1016/j.mad.2020.111345. [DOI] [PubMed] [Google Scholar]
44.Singh S, Singh RK. Recent advancements in the understanding of the alterations in mitochondrial biogenesis in Alzheimer’s disease. Mol Biol Rep 2025;52:173. doi: 10.1007/s11033-025-10297-6. [DOI] [PubMed] [Google Scholar]
45.Kumar M Acevedo-Cintron J Jhaldiyal A Wang H Andrabi SA Eacker S, et al. Defects in mitochondrial biogenesis drive mitochondrial alterations in parkin-deficient human dopamine neurons. Stem Cell Reports 2020;15:629-645. doi: 10.1016/j.stemcr.2020.07.013. [DOI] [PMC free article] [PubMed] [Google Scholar]
46.Wang H Chen R Xiao L Kumar M Acevedo-Cintron J Siuda J, et al. Defects in mitochondrial biogenesis drive mitochondrial alterations in PINK1-deficient human dopamine neurons. bioRxiv 2023. doi: 10.1101/2023.06.23.546087. [DOI] [PMC free article] [PubMed] [Google Scholar]
47.Han X Zhang M Daowei L Liu L Ma X Xiong Y, et al. PGC-1 alpha regulates mitochondrial biogenesis to promote silica-induced pulmonary fibrosis. Toxicol Res (Camb) 2025;14:tfaf070. doi: 10.1093/toxres/tfaf070. [DOI] [PMC free article] [PubMed] [Google Scholar]
48.Hwang JH Kim KM Oh HT Yoo GD Jeong MG Lee H, et al. TAZ links exercise to mitochondrial biogenesis via mitochondrial transcription factor A. Nat Commun 2022;13:653. doi: 10.1038/s41467-022-28247-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
49.Oliveira AN, Richards BJ, Slavin M, Hood DA. Exercise is muscle mitochondrial medicine. Exerc Sport Sci Rev 2021;49:67-76. doi: 10.1249/JES.0000000000000250. [DOI] [PubMed] [Google Scholar]
50.Chodari L Dilsiz Aytemir M Vahedi P Alipour M Vahed SZ Khatibi SMH, et al. Targeting mitochondrial biogenesis with polyphenol compounds. Oxid Med Cell Longev 2021;2021:4946711. doi: 10.1155/2021/4946711. [DOI] [PMC free article] [PubMed] [Google Scholar]
51.Hinkle JS, Rivera CN, Vaughan RA. Branched-chain amino acids and mitochondrial biogenesis: An overview and mechanistic summary. Mol Nutr Food Res 2022;66:e2200109. doi: 10.1002/mnfr.202200109. [DOI] [PMC free article] [PubMed] [Google Scholar]
52.Alzhrani RF, Alhowyan AA, Taha EI, Attia SM, Salama SA, Harisa GI. Medication targeting to subcellular organelles: Emphasizing mitochondria as a therapeutic marvel-Current situation and future prospects. Exp Cell Res 2025;450:114647. doi: 10.1016/j.yexcr.2025.114647. [DOI] [PubMed] [Google Scholar]
53.Green A, Hossain T, Eckmann DM. Mitochondrial dynamics involves molecular and mechanical events in motility, fusion and fission. Front Cell Dev Biol 2022;10:1010232. doi: 10.3389/fcell.2022.1010232. [DOI] [PMC free article] [PubMed] [Google Scholar]
54.Al Ojaimi M, Salah A, El-Hattab AW. Mitochondrial fission and fusion: Molecular mechanisms, biological functions, and related disorders. Membranes (Basel) 2022;12:893. doi: 10.3390/membranes12090893. [DOI] [PMC free article] [PubMed] [Google Scholar]
55.Adebayo M, Singh S, Singh AP, Dasgupta S. Mitochondrial fusion and fission: The fine-tune balance for cellular homeostasis. FASEB J 2021;35:e21620. doi: 10.1096/fj.202100067R. [DOI] [PMC free article] [PubMed] [Google Scholar]
56.Wisniewski BT, Lackner LL. Significantly reduced, but balanced, rates of mitochondrial fission and fusion are sufficient to maintain the integrity of yeast mitochondrial DNA. bioRxiv 2024:2024.07.18.604121. doi: 10.1101/2024.07.18.604121. [DOI] [PMC free article] [PubMed] [Google Scholar]
57.Wisniewski BT, Casler JC, Lackner LL. Significantly reduced, but balanced, rates of mitochondrial fission and fusion are sufficient to maintain the integrity of yeast mitochondrial DNA. Mol Biol Cell 2024;35:br25. doi: 10.1091/mbc.E24-07-0306. [DOI] [PMC free article] [PubMed] [Google Scholar]
58.Gu H, Yang K, Wu Q, Shen Z, Li X, Sun C. A link between protein acetylation and mitochondrial dynamics under energy metabolism: A comprehensive overview. J Cell Physiol 2021;236:7926-7937. doi: 10.1002/jcp.30461. [DOI] [PubMed] [Google Scholar]
59.Uddin GM, Abbas R, Shutt TE. The role of protein acetylation in regulating mitochondrial fusion and fission. Biochem Soc Trans 2021;49:2807-2819. doi: 10.1042/BST20210798. [DOI] [PubMed] [Google Scholar]
60.Wu Z, Xiao C, Li F, Huang W, You F, Li X. Mitochondrial fusion-fission dynamics and its involvement in colorectal cancer. Mol Oncol 2024;18:1058-1075. doi: 10.1002/1878-0261.13578. [DOI] [PMC free article] [PubMed] [Google Scholar]
61.Wu Z, Xiao C, Long J, Huang W, You F, Li X. Mitochondrial dynamics and colorectal cancer biology: Mechanisms and potential targets. Cell Commun Signal 2024;22:91. doi: 10.1186/s12964-024-01490-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
62.Ren L, Chen X, Chen X, Li J, Cheng B, Xia J. Mitochondrial dynamics: Fission and fusion in fate determination of mesenchymal stem cells. Front Cell Dev Biol 2020;8:580070. doi: 10.3389/fcell.2020.580070. [DOI] [PMC free article] [PubMed] [Google Scholar]
63.Grel H Woznica D Ratajczak K Kalwarczyk E Anchimowicz J Switlik W, et al. Mitochondrial dynamics in neurodegenerative diseases: Unraveling the role of fusion and fission processes. Int J Mol Sci 2023;24:13033. doi: 10.3390/ijms241713033. [DOI] [PMC free article] [PubMed] [Google Scholar]
64.Liu X, Guo C, Zhang Q. Novel insights into the involvement of mitochondrial fission/fusion in heart failure: From molecular mechanisms to targeted therapies. Cell Stress Chaperones 2023;28:133-144. doi: 10.1007/s12192-023-01321-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
65.Liu X, Li T, Tu X, Xu M, Wang J. Mitochondrial fission and fusion in neurodegenerative diseases: Ca(2+) signalling. Mol Cell Neurosci 2025;132:103992. doi: 10.1016/j.mcn.2025.103992. [DOI] [PubMed] [Google Scholar]
66.Yu R Liu T Jin SB Ankarcrona M Lendahl U Nister M, et al. MIEF1/2 orchestrate mitochondrial dynamics through direct engagement with both the fission and fusion machineries. BMC Biol 2021;19:229. doi: 10.1186/s12915-021-01161-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
67.Tran DT Tu Z Alawieh A Mulligan J Esckilsen S Quinn K, et al. Modulating donor mitochondrial fusion/fission delivers immunoprotective effects in cardiac transplantation. Am J Transplant 2022;22:386-401. doi: 10.1111/ajt.16882. [DOI] [PMC free article] [PubMed] [Google Scholar]
68.Fang Y, Min S, Shen H. The role of mitochondrial fusion and fission in immune-mediated inflammatory diseases. Cell Immunol 2024;403–404:104864. doi: 10.1016/j.cellimm.2024.104864. [DOI] [PubMed] [Google Scholar]
69.Iqbal U, Malik A, Ibrahim L, Sial NT, Mehmood MH. Natural and synthetic potential drug leads for rheumatoid arthritis probing innovative target: Mitochondrial dysfunction and NLRP3 inflammasome activation. Naunyn Schmiedebergs Arch Pharmacol 2025;398:8295-8312. doi: 10.1007/s00210-025-03897-3. [DOI] [PubMed] [Google Scholar]
70.Li P Wang G Peng Z Zhang L Yang F Wei Y, et al. The role of mitochondrial regulation in macrophage polarization: Implications for the pathogenesis of rheumatoid arthritis. J Inflamm Res 2025;18:17163-17183. doi: 10.2147/JIR.S560635. [DOI] [PMC free article] [PubMed] [Google Scholar]
71.Chen S Liu X Zhang W Li B Liu F Zhang Y, et al. Nanozyme coating-mediated mitochondrial metabolic reprogramming of macrophages for immunomodulatory osseointegration in rheumatoid arthritis case. ACS Nano 2025;19:26127-26146. doi: 10.1021/acsnano.5c07535. [DOI] [PubMed] [Google Scholar]
72.Jiang X Lu Z Zhang Q Yu J Han D Liu J, et al. Osthole: A potential AMPK agonist that inhibits NLRP3 inflammasome activation by regulating mitochondrial homeostasis for combating rheumatoid arthritis. Phytomedicine 2023;110:154640. doi: 10.1016/j.phymed.2022.154640. [DOI] [PubMed] [Google Scholar]
73.Wang S Zhao H Lin S Lv Y Lin Y Liu Y, et al. New therapeutic directions in type II diabetes and its complications: Mitochondrial dynamics. Front Endocrinol (Lausanne) 2023;14:1230168. doi: 10.3389/fendo.2023.1230168. [DOI] [PMC free article] [PubMed] [Google Scholar]
74.Narendra DP, Youle RJ. The role of PINK1-Parkin in mitochondrial quality control. Nat Cell Biol 2024;26:1639-1651. doi: 10.1038/s41556-024-01513-9. [DOI] [PubMed] [Google Scholar]
75.Basak B, Holzbaur ELF. Mitophagy in neurons: Mechanisms regulating mitochondrial turnover and neuronal homeostasis. J Mol Biol 2025;437:169161. doi: 10.1016/j.jmb.2025.169161. [DOI] [PubMed] [Google Scholar]
76.Chandra S, Katiyar P, Durairaj AS, Wang X. Mitochondrial calcium transport during autophagy initiation. Mitochondrial Commun 2024;2:14-20. doi: 10.1016/j.mitoco.2024.01.002. [DOI] [PMC free article] [PubMed] [Google Scholar]
77.Wu D, Ji H, Du W, Ren L, Qian G. Mitophagy alleviates ischemia/reperfusion-induced microvascular damage through improving mitochondrial quality control. Bioengineered 2022;13:3596-3607. doi: 10.1080/21655979.2022.2027065. [DOI] [PMC free article] [PubMed] [Google Scholar]
78.Fu T, Ma Y, Li Y, Wang Y, Wang Q, Tong Y. Mitophagy as a mitochondrial quality control mechanism in myocardial ischemic stress: From bench to bedside. Cell Stress Chaperones 2023;28:239-251. doi: 10.1007/s12192-023-01346-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
79.Picca A, Calvani R, Coelho-Junior HJ, Marzetti E. Mitophagy: At the heart of mitochondrial quality control in cardiac aging and frailty. Exp Gerontol 2021;153:111508. doi: 10.1016/j.exger.2021.111508. [DOI] [PubMed] [Google Scholar]
80.Tang Y, Xu W, Liu Y, Zhou J, Cui K, Chen Y. Autophagy protects mitochondrial health in heart failure. Heart Fail Rev 2024;29:113-123. doi: 10.1007/s10741-023-10354-x. [DOI] [PubMed] [Google Scholar]
81.Song Y Xu Y Liu Y Gao J Feng L Zhang Y, et al. Mitochondrial quality control in the maintenance of cardiovascular homeostasis: The roles and interregulation of ups, mitochondrial dynamics and mitophagy. Oxid Med Cell Longev 2021;2021:3960773. doi: 10.1155/2021/3960773. [DOI] [PMC free article] [PubMed] [Google Scholar]
82.Haeussler S Kohler F Witting M Premm MF Rolland SG Fischer C, et al. Autophagy compensates for defects in mitochondrial dynamics. PLoS Genet 2020;16:e1008638. doi: 10.1371/journal.pgen.1008638. [DOI] [PMC free article] [PubMed] [Google Scholar]
83.Braun MM, Puglielli L. Defective PTEN-induced kinase 1/Parkin mediated mitophagy and neurodegenerative diseases. Front Cell Neurosci 2022;16:1031153. doi: 10.3389/fncel.2022.1031153. [DOI] [PMC free article] [PubMed] [Google Scholar]
84.Dernie F. Mitophagy in Parkinson’s disease: From pathogenesis to treatment target. Neurochem Int 2020;138:104756. doi: 10.1016/j.neuint.2020.104756. [DOI] [PubMed] [Google Scholar]
85.Cen X, Zhang M, Zhou M, Ye L, Xia H. Mitophagy regulates neurodegenerative diseases. Cells 2021;10:1876. doi: 10.3390/cells10081876. [DOI] [PMC free article] [PubMed] [Google Scholar]
86.Cai Q, Jeong YY. Mitophagy in Alzheimer’s disease and other age-related neurodegenerative diseases. Cells 2020;9:150. doi: 10.3390/cells9010150. [DOI] [PMC free article] [PubMed] [Google Scholar]
87.Banarase TA Sammeta SS Wankhede NL Mangrulkar SV Rahangdale SR Aglawe MM, et al. Mitophagy regulation in aging and neurodegenerative disease. Biophys Rev 2023;15:239-255. doi: 10.1007/s12551-023-01057-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
88.Yuk JM, Silwal P, Jo EK. Inflammasome and mitophagy connection in health and disease. Int J Mol Sci 2020;21:4714. doi: 10.3390/ijms21134714. [DOI] [PMC free article] [PubMed] [Google Scholar]
89.Mauri S, Favaro M, Bernardo G, Mazzotta GM, Ziviani E. Mitochondrial autophagy in the sleeping brain. Front Cell Dev Biol 2022;10:956394. doi: 10.3389/fcell.2022.956394. [DOI] [PMC free article] [PubMed] [Google Scholar]
90.Bakula D, Scheibye-Knudsen M. MitophAging: Mitophagy in aging and disease. Front Cell Dev Biol 2020;8:239. doi: 10.3389/fcell.2020.00239. [DOI] [PMC free article] [PubMed] [Google Scholar]
91.Zeng Z, Liang J, Wu L, Zhang H, Lv J, Chen N. Exercise-induced autophagy suppresses sarcopenia through Akt/mTOR and Akt/FoxO3a signal pathways and AMPK-mediated mitochondrial quality control. Front Physiol 2020;11:583478. doi: 10.3389/fphys.2020.583478. [DOI] [PMC free article] [PubMed] [Google Scholar]
92.Gomora-Garcia JC Montiel T Huttenrauch M Salcido-Gomez A Garcia-Velazquez L Ramiro-Cortes Y, et al. Effect of the ketone body, D-beta-hydroxybutyrate, on sirtuin2-mediated regulation of mitochondrial quality control and the autophagy-lysosomal pathway. Cells 2023;12:486. doi: 10.3390/cells12030486. [DOI] [PMC free article] [PubMed] [Google Scholar]
93.Liu Z Qin G Yang J Wang W Zhang W Lu B, et al. Targeting mitochondrial degradation by chimeric autophagy-tethering compounds. Chem Sci 2023;14:11192-11202. doi: 10.1039/d3sc03600f. [DOI] [PMC free article] [PubMed] [Google Scholar]
94.Kim JS, Chapman WC, Lin Y. Mitochondrial autophagy in ischemic aged livers. Cells 2022;11:4083. doi: 10.3390/cells11244083. [DOI] [PMC free article] [PubMed] [Google Scholar]
95.Wang C, Wang Y. The role and mechanism of action of mitophagy in various liver diseases. Antioxid Redox Signal 2023;38:529-549. doi: 10.1089/ars.2022.0114. [DOI] [PubMed] [Google Scholar]
96.Dantas WS Zunica ERM Heintz EC Vandanmagsar B Floyd ZE Yu Y, et al. Mitochondrial uncoupling attenuates sarcopenic obesity by enhancing skeletal muscle mitophagy and quality control. J Cachexia Sarcopenia Muscle 2022;13:1821-1836. doi: 10.1002/jcsm.12982. [DOI] [PMC free article] [PubMed] [Google Scholar]
97.Hou GZ, Guo Q, Han PP. Autophagy activation and mitochondrial quality control in sarcopenia (in Chinese). Acta Academiae Medicinae Sinicae 2022;44:709-716. doi: 10.3881/j.issn.1000-503X.13753. [DOI] [PubMed] [Google Scholar]
98.Liu M Chen J Sun M Zhang L Yu Y Mi W, et al. Protection of Ndrg2 deficiency on renal ischemia-reperfusion injury via activating PINK1/Parkin-mediated mitophagy. Chin Med J 2024;137:2603-2614. doi: 10.1097/CM9.0000000000002957. [DOI] [PMC free article] [PubMed] [Google Scholar]
99.Tang X Zhang A Feng X Wang W Chen F Tao Y, et al. Global research trends on the associations between chronic kidney disease and mitochondria: Insights from the bibliometric analysis. Int Urol Nephrol 2025;57:2579-2594. doi: 10.1007/s11255-025-04437-x. [DOI] [PubMed] [Google Scholar]
100.Wei X Wang Y Lao Y Weng J Deng R Li S, et al. Effects of honokiol protects against chronic kidney disease via BNIP3/NIX and FUNDC1-mediated mitophagy and AMPK pathways. Mol Biol Rep 2023;50:6557-6568. doi: 10.1007/s11033-023-08592-1. [DOI] [PubMed] [Google Scholar]
101.Aranda-Rivera AK Amador-Martinez I Aparicio-Trejo OE Leon-Contreras JC Hernandez-Pando R Saavedra E, et al. Sulforaphane restores mitochondrial beta-oxidation and reduces renal lipid accumulation in a model of releasing unilateral ureteral obstruction. Antioxidants (Basel) 2025;14:288. doi: 10.3390/antiox14030288. [DOI] [PMC free article] [PubMed] [Google Scholar]
102.Jia Q Han L Zhang X Yang W Gao Y Shen Y, et al. Tongluo yishen decoction ameliorates renal fibrosis via regulating mitochondrial dysfunction induced by oxidative stress in unilateral ureteral obstruction rats. Front Pharmacol 2021;12:762756. doi: 10.3389/fphar.2021.762756. [DOI] [PMC free article] [PubMed] [Google Scholar]
103.Wu Y Yang F Zhou G Wang Q Xing C Bai H, et al. Molybdenum and cadmium co-induce mitochondrial quality control disorder via FUNDC1-mediated mitophagy in sheep kidney. Front Vet Sci 2022;9:842259. doi: 10.3389/fvets.2022.842259. [DOI] [PMC free article] [PubMed] [Google Scholar]
104.Wang L Duan Z Liang M Wang C Liang T Sun L, et al. A pivotal role of selective autophagy in mitochondrial quality control: Implications for zinc oxide nanoparticles induced neurotoxicity. Chem Biol Interact 2022;363:110003. doi: 10.1016/j.cbi.2022.110003. [DOI] [PubMed] [Google Scholar]
105.Javaid HMA, Lim H, Shin S, Huh JY. Inhibition of autophagy with chloroquine dysregulates mitochondrial quality control and energetics in adipocytes. Arch Pharm Res 2022;45:731-742. doi: 10.1007/s12272-022-01412-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
106.Sasaki Y, Ikeda Y, Uchikado Y, Akasaki Y, Sadoshima J, Ohishi M. Estrogen plays a crucial role in Rab9-dependent mitochondrial autophagy, delaying arterial senescence. J Am Heart Assoc 2021;10:e019310. doi: 10.1161/JAHA.120.019310. [DOI] [PMC free article] [PubMed] [Google Scholar]
107.Xu Z Fu T Guo Q Zhou D Sun W Zhou Z, et al. Disuse-associated loss of the protease LONP1 in muscle impairs mitochondrial function and causes reduced skeletal muscle mass and strength. Nat Commun 2022;13:894. doi: 10.1038/s41467-022-28557-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
108.Uchikado Y, Ikeda Y, Sasaki Y, Iwabayashi M, Akasaki Y, Ohishi M. Association of Lectin-like oxidized low-density lipoprotein receptor-1 with angiotensin II type 1 receptor impacts mitochondrial quality control, offering promise for the treatment of vascular senescence. Front Cardiovasc Med 2021;8:788655. doi: 10.3389/fcvm.2021.788655. [DOI] [PMC free article] [PubMed] [Google Scholar]
109.Towers CG, Wodetzki DK, Thorburn J, Smith KR, Caino MC, Thorburn A. Mitochondrial-derived vesicles compensate for loss of LC3-mediated mitophagy. Dev Cell 2021;56:2029-2042.e25. doi: 10.1016/j.devcel.2021.06.003. [DOI] [PMC free article] [PubMed] [Google Scholar]
110.Shin CS Meng S Garbis SD Moradian A Taylor RW Sweredoski MJ, et al. LONP1 and mtHSP70 cooperate to promote mitochondrial protein folding. Nat Commun 2021;12:265. doi: 10.1038/s41467-020-20597-z. [DOI] [PMC free article] [PubMed] [Google Scholar]
111.Kan KT, Wilcock J, Lu H. Role of Yme1 in mitochondrial protein homeostasis: From regulation of protein import, OXPHOS function to lipid synthesis and mitochondrial dynamics. Biochem Soc Trans 2024;52:1539-1548. doi: 10.1042/BST20240450. [DOI] [PMC free article] [PubMed] [Google Scholar]
112.Li J Zhu J Deng Y Reck EC Walker EM Sidarala V, et al. LONP1 regulation of mitochondrial protein folding provides insight into beta cell failure in type 2 diabetes. bioRxiv 2024;2024.06.03.597215. doi: 10.1101/2024.06.03.597215. [DOI] [PMC free article] [PubMed] [Google Scholar]
113.Rolland S, Conradt B. Genetic screen identifies non-mitochondrial proteins involved in the maintenance of mitochondrial homeostasis. MicroPubl Biol 2022;2022:10.17912/micropub.biology.000562. doi: 10.17912/micropub.biology.000562. [DOI] [PMC free article] [PubMed] [Google Scholar]
114.Cilleros-Holgado P Gomez-Fernandez D Pinero-Perez R Romero-Dominguez JM Reche-Lopez D Lopez-Cabrera A, et al. Mitochondrial quality control via mitochondrial unfolded protein response (mtUPR) in ageing and neurodegenerative diseases. Biomolecules 2023;13:1789. doi: 10.3390/biom13121789. [DOI] [PMC free article] [PubMed] [Google Scholar]
115.Yang M Luo S Chen W He L Liu D Wang X, et al. Mitochondrial unfolded protein response (mtUPR) and diseases. Curr Med Chem 2025;32:1674-1684. doi: 10.2174/0929867331666230822095924. [DOI] [PubMed] [Google Scholar]
116.Haynes CM, Hekimi S. Mitochondrial dysfunction, aging, and the mitochondrial unfolded protein response in Caenorhabditis elegans. Genetics 2022;222:iyac160. doi: 10.1093/genetics/iyac160. [DOI] [PMC free article] [PubMed] [Google Scholar]
117.Zhou Z Lu J Yang M Cai J Fu Q Ma J, et al. The mitochondrial unfolded protein response (UPR(mt)) protects against osteoarthritis. Exp Mol Med 2022;54:1979-1990. doi: 10.1038/s12276-022-00885-y. [DOI] [PMC free article] [PubMed] [Google Scholar]
118.Deng J Wang D Shi Y Lin L Gao W Sun Y, et al. Mitochondrial unfolded protein response mechanism and its cardiovascular protective effects. Biomed Pharmacother 2024;177:116989. doi: 10.1016/j.biopha.2024.116989. [DOI] [PubMed] [Google Scholar]
119.Maruszczak KK, Ayyamperumal S, Chacinska A. Defective mitochondrial import as a challenge for cellular protein homeostasis. FEBS Lett 2023;597:1555-1568. doi: 10.1002/1873-3468.14677. [DOI] [PubMed] [Google Scholar]
120.Lee-Glover LP, Shutt TE. Mitochondrial quality control pathways sense mitochondrial protein import. Trends Endocrinol Metab 2024;35:308-320. doi: 10.1016/j.tem.2023.11.004. [DOI] [PubMed] [Google Scholar]
121.Balzarini M, Kim J, Weidberg H. Quality control of un-imported mitochondrial proteins at a glance. J Cell Sci 2025;138:jcs263757. doi: 10.1242/jcs.263757. [DOI] [PubMed] [Google Scholar]
122.Hu L Li J Guo H Su L Dong P Huang J, et al. SENP6 maintains mitochondrial homeostasis by regulating mitochondrial protein import through deSUMOylation of TOM40. Adv Sci (Weinh) 2025;12:e03408. doi: 10.1002/advs.202503408. [DOI] [PMC free article] [PubMed] [Google Scholar]
123.Nowicka U Chroscicki P Stroobants K Sladowska M Turek M Uszczynska-Ratajczak B, et al. Cytosolic aggregation of mitochondrial proteins disrupts cellular homeostasis by stimulating the aggregation of other proteins. eLife 2021;10:e65484. doi: 10.7554/eLife.65484. [DOI] [PMC free article] [PubMed] [Google Scholar]
124.Jenkins EC, Chattopadhyay M, Germain D. Folding mitochondrial-mediated cytosolic proteostasis into the mitochondrial unfolded protein response. Front Cell Dev Biol 2021;9:715923. doi: 10.3389/fcell.2021.715923. [DOI] [PMC free article] [PubMed] [Google Scholar]
125.Felipe Perez R, Mochi G, Khan A, Woodford M. Mitochondrial chaperone code: Just warming up. Cell Stress Chaperones 2024;29:483-496. doi: 10.1016/j.cstres.2024.05.002. [DOI] [PMC free article] [PubMed] [Google Scholar]
126.Konovalova S Torregrosa-Munumer R Manjunath P Liu X Baral S Fatima K, et al. Small mitochondrial protein NERCLIN regulates cardiolipin homeostasis and mitochondrial ultrastructure. Proc Natl Acad Sci U S A 2023;120:e2210599120. doi: 10.1073/pnas.2210599120. [DOI] [PMC free article] [PubMed] [Google Scholar]
127.Wachoski-Dark E, Zhao T, Khan A, Shutt TE, Greenway SC. Mitochondrial protein homeostasis and cardiomyopathy. Int J Mol Sci 2022;23:3353. doi: 10.3390/ijms23063353. [DOI] [PMC free article] [PubMed] [Google Scholar]
128.Zhao T Goedhart C Pfeffer G Greenway SC Lines M Khan A, et al. Skeletal phenotypes due to abnormalities in mitochondrial protein homeostasis and import. Int J Mol Sci 2020;21:8327. doi: 10.3390/ijms21218327. [DOI] [PMC free article] [PubMed] [Google Scholar]
129.Jishi A, Qi X. Altered mitochondrial protein homeostasis and proteinopathies. Front Mol Neurosci 2022;15:867935. doi: 10.3389/fnmol.2022.867935. [DOI] [PMC free article] [PubMed] [Google Scholar]
130.Jagtap YA Kumar P Kinger S Dubey AR Choudhary A Gutti RK, et al. Disturb mitochondrial associated proteostasis: Neurodegeneration and imperfect ageing. Front Cell Dev Biol 2023;11:1146564. doi: 10.3389/fcell.2023.1146564. [DOI] [PMC free article] [PubMed] [Google Scholar]
131.Guo J Wang Y Zhang D Shi C Zhang X Li X, et al. The FMO3/TMAO/HSP90beta axis aggravates MAFLD by disrupting mitochondrial protein homeostasis. Cell Signal 2025;134:111960. doi: 10.1016/j.cellsig.2025.111960. [DOI] [PubMed] [Google Scholar]
132.Lima TI Laurila PP Wohlwend M Morel JD Goeminne LJE Li H, et al. Inhibiting de novo ceramide synthesis restores mitochondrial and protein homeostasis in muscle aging. Sci Transl Med 2023;15:eade6509. doi: 10.1126/scitranslmed.ade6509. [DOI] [PubMed] [Google Scholar]
133.Molenaars M, Daniels EG, Meurs A, Janssens GE, Houtkooper RH. Mitochondrial cross-compartmental signalling to maintain proteostasis and longevity. Philos Trans R Soc Lond B Biol Sci 2020;375:20190414. doi: 10.1098/rstb.2019.0414. [DOI] [PMC free article] [PubMed] [Google Scholar]
134.Baker MJ, Yek KQ, Stojanovski D. Quality control at the powerhouse: Mitochondrial proteostasis dysfunction and disease. Biochem Soc Trans 2025;53:1-13. doi: 10.1042/BST20253044. [DOI] [PMC free article] [PubMed] [Google Scholar]
135.Madrazo N, Khattar Z, Powers ET, Rosarda JD, Wiseman RL. Mapping stress-responsive signaling pathways induced by mitochondrial proteostasis perturbations. Mol Biol Cell 2024;35:ar74. doi: 10.1091/mbc.E24-01-0041. [DOI] [PMC free article] [PubMed] [Google Scholar]
136.Popov LD. Mitochondrial-derived vesicles: Recent insights. J Cell Mol Med 2022;26:3323-3328. doi: 10.1111/jcmm.17391. [DOI] [PMC free article] [PubMed] [Google Scholar]
137.Peng T, Xie Y, Sheng H, Wang C, Lian Y, Xie N. Mitochondrial-derived vesicles: Gatekeepers of mitochondrial response to oxidative stress. Free Radic Biol Med 2022;188:185-193. doi: 10.1016/j.freeradbiomed.2022.06.233. [DOI] [PubMed] [Google Scholar]
138.Tang M Tu Y Gong Y Yang Q Wang J Zhang Z, et al. Beta-hydroxybutyrate facilitates mitochondrial-derived vesicle biogenesis and improves mitochondrial functions. Mol Cell 2025;85:1395-1410.e95. doi: 10.1016/j.molcel.2025.02.022. [DOI] [PubMed] [Google Scholar]
139.Sekine S, Sekine Y. Metabolite tunes MDV pathway to maintain mitochondrial fitness. Mol Cell 2025;85:1253-1255. doi: 10.1016/j.molcel.2025.02.027. [DOI] [PubMed] [Google Scholar]
140.Bao F, Zeng D, Xiao J, Zhou L, Liu X. Beta-hydroxybutyrate enhances mitochondrial function via mitochondrial-derived vesicles. Sci Bull (Beijing) 2025;70:3100-3102. doi: 10.1016/j.scib.2025.05.011. [DOI] [PubMed] [Google Scholar]
141.Konig T Nolte H Aaltonen MJ Tatsuta T Krols M Stroh T, et al. MIROs and DRP1 drive mitochondrial-derived vesicle biogenesis and promote quality control. Nat Cell Biol 2021;23:1271-1286. doi: 10.1038/s41556-021-00798-4. [DOI] [PubMed] [Google Scholar]
142.Konig T, McBride HM. Mitochondrial-derived vesicles in metabolism, disease, and aging. Cell Metab 2024;36:21-35. doi: 10.1016/j.cmet.2023.11.014. [DOI] [PubMed] [Google Scholar]
143.Ryan TA Phillips EO Collier CL Jb Robinson A Routledge D Wood RE, et al. Tollip coordinates Parkin-dependent trafficking of mitochondrial-derived vesicles. EMBO J 2020;39:e102539. doi: 10.15252/embj.2019102539. [DOI] [PMC free article] [PubMed] [Google Scholar]
144.Mondal P, Towers C. Beyond mitophagy: Mitochondrial-derived vesicles can get the job done! Autophagy 2022;18:449-451. doi: 10.1080/15548627.2021.1999562. [DOI] [PMC free article] [PubMed] [Google Scholar]
145.Li B Zhao H Wu Y Zhu Y Zhang J Yang G, et al. Mitochondrial-derived vesicles protect cardiomyocytes against hypoxic damage. Front Cell Dev Biol 2020;8:214. doi: 10.3389/fcell.2020.00214. [DOI] [PMC free article] [PubMed] [Google Scholar]
146.Heyn J, Heuschkel MA, Goettsch C. Mitochondrial-derived vesicles-link to extracellular vesicles and implications in cardiovascular disease. Int J Mol Sci 2023;24:3100-3102. doi: 10.3390/ijms24032637. [DOI] [PMC free article] [PubMed] [Google Scholar]
147.Kong J Sun R Du C Tang Y Xie C Li Q, et al. Mitochondrial extracellular vesicles: A novel approach to mitochondrial quality control. Biomolecules 2025;15:1145. doi: 10.3390/biom15081145. [DOI] [PMC free article] [PubMed] [Google Scholar]
148.Iorio R, Petricca S, Di Emidio G, Falone S, Tatone C. Mitochondrial extracellular vesicles (mitoEVs): Emerging mediators of cell-to-cell communication in health, aging and age-related diseases. Ageing Res Rev 2024;101:102522. doi: 10.1016/j.arr.2024.102522. [DOI] [PubMed] [Google Scholar]
149.Allan HE Dark N Vulliamy P Crescente M Maffucci T Armstrong PC, et al. Platelet mitochondrial transfer via extracellular vesicles modulates neutrophil phenotype and function. J Thromb Haemost 2025;23:3665-3677. doi: 10.1016/j.jtha.2025.08.004. [DOI] [PubMed] [Google Scholar]
150.Ferrucci L, Guerra F, Bucci C, Marzetti E, Picca A. Mitochondria break free: Mitochondria-derived vesicles in aging and associated conditions. Ageing Res Rev 2024;102:102549. doi: 10.1016/j.arr.2024.102549. [DOI] [PMC free article] [PubMed] [Google Scholar]
151.Hong WL, Huang H, Zeng X, Duan CY. Targeting mitochondrial quality control: New therapeutic strategies for major diseases. Mil Med Res 2024;11:59. doi: 10.1186/s40779-024-00556-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
152.Beatriz M Vilaca R Anjo SI Manadas B Januario C Rego AC, et al. Defective mitochondria-lysosomal axis enhances the release of extracellular vesicles containing mitochondrial DNA and proteins in Huntington’s disease. J Extracell Biol 2022;1:e65. doi: 10.1002/jex2.65. [DOI] [PMC free article] [PubMed] [Google Scholar]
153.Garesse R, Vallejo CG. Animal mitochondrial biogenesis and function: A regulatory cross-talk between two genomes. Gene 2001;263:1-16. doi: 10.1016/s0378-1119(00)00582-5. [DOI] [PubMed] [Google Scholar]
154.Allkanjari K, Baldock RA. Beyond base excision repair: An evolving picture of mitochondrial DNA repair. Biosci Rep 2021;41:BSR20211320. doi: 10.1042/BSR20211320. [DOI] [PMC free article] [PubMed] [Google Scholar]
155.LeDoux SP, Druzhyna NM, Hollensworth SB, Harrison JF, Wilson GL. Mitochondrial DNA repair: A critical player in the response of cells of the CNS to genotoxic insults. Neuroscience 2007;145:1249-1259. doi: 10.1016/j.neuroscience.2006.10.002. [DOI] [PMC free article] [PubMed] [Google Scholar]
156.Lu J, Li Y, Mollinari C, Garaci E, Merlo D, Pei G. Amyloid-beta oligomers-induced mitochondrial DNA repair impairment contributes to altered human neural stem cell differentiation. Curr Alzheimer Res 2019;16:934-949. doi: 10.2174/1567205016666191023104036. [DOI] [PubMed] [Google Scholar]
157.Ngo HB, Lovely GA, Phillips R, Chan DC. Distinct structural features of TFAM drive mitochondrial DNA packaging versus transcriptional activation. Nat Commun 2014;5:3077. doi: 10.1038/ncomms4077. [DOI] [PMC free article] [PubMed] [Google Scholar]
158.Frandsen JR Yuan Z Bedi B Prasla Z Choi SR Narayanasamy P, et al. PGC-1alpha activation to enhance macrophage immune function in mycobacterial infections. PLoS One 2025;20:e0310908. doi: 10.1371/journal.pone.0310908. [DOI] [PMC free article] [PubMed] [Google Scholar]
159.Kumagai H Miller B Kim SJ Leelaprachakul N Kikuchi N Yen K, et al. Novel insights into mitochondrial DNA: Mitochondrial microproteins and mtDNA variants modulate athletic performance and age-related diseases. Genes (Basel) 2023;14:286. doi: 10.3390/genes14020286. [DOI] [PMC free article] [PubMed] [Google Scholar]
160.Lee C, Kim KH, Cohen P. MOTS-c: A novel mitochondrial-derived peptide regulating muscle and fat metabolism. Free Radic Biol Med 2016;100:182-187. doi: 10.1016/j.freeradbiomed.2016.05.015. [DOI] [PMC free article] [PubMed] [Google Scholar]
161.Chen S Bao X Chen H Jia M Li W Zhang L, et al. Thyroid cancer-associated mitochondrial DNA mutation G3842A promotes tumorigenicity via ROS-mediated ERK1/2 activation. Oxid Med Cell Longev 2022;2022:9982449. doi: 10.1155/2022/9982449. [DOI] [PMC free article] [PubMed] [Google Scholar]
162.Tsybrovskyy O De Luise M de Biase D Caporali L Fiorini C Gasparre G, et al. Papillary thyroid carcinoma tall cell variant shares accumulation of mitochondria, mitochondrial DNA mutations, and loss of oxidative phosphorylation complex I integrity with oncocytic tumors. J Pathol Clin Res 2022;8:155-168. doi: 10.1002/cjp2.247. [DOI] [PMC free article] [PubMed] [Google Scholar]
163.Kowluru RA, Kumar J, Malaviya P. DNA methylation of long noncoding RNA cytochrome B in diabetic retinopathy. Noncoding RNA Res 2025;11:141-149. doi: 10.1016/j.ncrna.2024.12.007. [DOI] [PMC free article] [PubMed] [Google Scholar]
164.Batsaikhan J Park KH Chang HR Jung E Kim MJ Kang J, et al. KU80 suppresses endonuclease G activity to preserve genomic integrity. FEBS J 2026. doi: 10.1111/febs.70495. [DOI] [PMC free article] [PubMed] [Google Scholar]
165.Feng Y, Lu Y. The nuclear-mitochondrial crosstalk in aging: From mechanisms to therapeutics. Free Radic Biol Med 2025;232:391-397. doi: 10.1016/j.freeradbiomed.2025.03.012. [DOI] [PubMed] [Google Scholar]
166.Perez-Trevino P, Velasquez M, Garcia N. Mechanisms of mitochondrial DNA escape and its relationship with different metabolic diseases. Biochim Biophys Acta Mol Basis Dis 2020;1866:165761. doi: 10.1016/j.bbadis.2020.165761. [DOI] [PubMed] [Google Scholar]
167.Saxena R de Bakker PI Singer K Mootha V Burtt N Hirschhorn JN, et al. Comprehensive association testing of common mitochondrial DNA variation in metabolic disease. Am J Hum Genet 2006;79:54-61. doi: 10.1086/504926. [DOI] [PMC free article] [PubMed] [Google Scholar]
168.Guo DF Merrill RA Qian L Hsu Y Zhang Q Lin Z, et al. The BBSome regulates mitochondria dynamics and function. Mol Metab 2023;67:101654. doi: 10.1016/j.molmet.2022.101654. [DOI] [PMC free article] [PubMed] [Google Scholar]
169.Jacob S Kosaka Y Bhatlekar S Denorme F Benzon H Moody A, et al. Mitofusin-2 regulates platelet mitochondria and function. Circ Res 2024;134:143-161. doi: 10.1161/CIRCRESAHA.123.322914. [DOI] [PMC free article] [PubMed] [Google Scholar]
170.Zhu R Liu L Mao T Wang X Li Y Li T, et al. Mfn2 regulates mitochondria and mitochondria-associated endoplasmic reticulum membrane function in neurodegeneration induced by repeated sevoflurane exposure. Exp Neurol 2024;377:114807. doi: 10.1016/j.expneurol.2024.114807. [DOI] [PubMed] [Google Scholar]
171.Li Y Huang D Jia L Shangguan F Gong S Lan L, et al. LonP1 links mitochondria-ER interaction to regulate heart function. Research (Wash D C) 2023;6:0175. doi: 10.34133/research.0175. [DOI] [PMC free article] [PubMed] [Google Scholar]
172.Harada T Sada R Osugi Y Matsumoto S Matsuda T Hayashi-Nishino M, et al. Palmitoylated CKAP4 regulates mitochondrial functions through an interaction with VDAC2 at ER-mitochondria contact sites. J Cell Sci 2020;133:jcs249045. doi: 10.1242/jcs.249045. [DOI] [PubMed] [Google Scholar]
173.Ravanelli S, den Brave F, Hoppe T. Mitochondrial quality control governed by ubiquitin. Front Cell Dev Biol 2020;8:270. doi: 10.3389/fcell.2020.00270. [DOI] [PMC free article] [PubMed] [Google Scholar]
174.Aphasizheva I, Aphasizhev R. Mitochondrial RNA quality control in trypanosomes. Wiley Interdiscip Rev RNA 2021;12:e1638. doi: 10.1002/wrna.1638. [DOI] [PMC free article] [PubMed] [Google Scholar]
175.Brzezniakiewicz-Janus K, Jarczak J, Konopko A, Ratajczak J, Kucia M, Ratajczak MZ. Mitochondria express functional signaling ligand-binding receptors that regulate their biological responses-The novel role of mitochondria as stress-response sentinels. Stem Cell Rev Rep 2025;21:597-604. doi: 10.1007/s12015-025-10847-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
176.Wu X Yi X Zhao B Zhi Y Xu Z Cao Y, et al. The volume regulated anion channel VRAC regulates NLRP3 inflammasome by modulating itaconate efflux and mitochondria function. Pharmacol Res 2023;198:107016. doi: 10.1016/j.phrs.2023.107016. [DOI] [PubMed] [Google Scholar]
177.Ledderose C, Junger WG. Mitochondria synergize with P2 receptors to regulate human T cell function. Front Immunol 2020;11:549889. doi: 10.3389/fimmu.2020.549889. [DOI] [PMC free article] [PubMed] [Google Scholar]
178.Wang ZH, Chen L, Li W, Chen L, Wang YP. Mitochondria transfer and transplantation in human health and diseases. Mitochondrion 2022;65:80-87. doi: 10.1016/j.mito.2022.05.002. [DOI] [PubMed] [Google Scholar]
179.Dong LF Rohlena J Zobalova R Nahacka Z Rodriguez AM Berridge MV, et al. Mitochondria on the move: Horizontal mitochondrial transfer in disease and health. J Cell Biol 2023;222:e202211044. doi: 10.1083/jcb.202211044. [DOI] [PMC free article] [PubMed] [Google Scholar]
180.Feng H Tian C Jiang W Sun Z Li Y Han B, et al. Hydrogen sulfide sustains mitochondria functions via targeting mitochondria fission regulator 1 like protein to restore human cytotrophoblast invasion and migration. Int J Biol Macromol 2025;299:140240. doi: 10.1016/j.ijbiomac.2025.140240. [DOI] [PubMed] [Google Scholar]
181.Zhou L, Wang Q. Advances of H(2)S in regulating neurodegenerative diseases by preserving mitochondria function. Antioxidants (Basel) 2023;12:652. doi: 10.3390/antiox12030652. [DOI] [PMC free article] [PubMed] [Google Scholar]
182.Ding Y Gui X Chu X Sun Y Zhang S Tong H, et al. MTH1 protects platelet mitochondria from oxidative damage and regulates platelet function and thrombosis. Nat Commun 2023;14:4829. doi: 10.1038/s41467-023-40600-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
183.Ikeda T, Watanabe S, Mitani T. Genistein regulates adipogenesis by blocking the function of adenine nucleotide translocase-2 in the mitochondria. Biosci Biotechnol Biochem 2022;86:260-272. doi: 10.1093/bbb/zbab203. [DOI] [PubMed] [Google Scholar]
184.Zhang MY, Zhang H, Yao YM, Yang DW. Kruppel-like factors in mitochondrial quality control. Front Physiol 2025;16:1554877. doi: 10.3389/fphys.2025.1554877. [DOI] [PMC free article] [PubMed] [Google Scholar]
185.Labbadia J. Potential roles for mitochondria-to-HSF1 signaling in health and disease. Front Mol Biosci 2023;10:1332658. doi: 10.3389/fmolb.2023.1332658. [DOI] [PMC free article] [PubMed] [Google Scholar]
186.Ye L, Fu X, Li Q. Mitochondrial quality control in health and disease. MedComm (2020) 2025;6:e70319. doi: 10.1002/mco2.70319. [DOI] [PMC free article] [PubMed] [Google Scholar]
187.Zheng Y Yang J Li X Qi L Zheng Z Kong J, et al. Mitochondria at the crossroads: Quality control mechanisms in neuronal senescence and neurodegeneration. Neurobiol Dis 2025;208:106862. doi: 10.1016/j.nbd.2025.106862. [DOI] [PubMed] [Google Scholar]
188.Fan H He Z Huang H Zhuang H Liu H Liu X, et al. Mitochondrial quality control in cardiomyocytes: A critical role in the progression of cardiovascular diseases. Front Physiol 2020;11:252. doi: 10.3389/fphys.2020.00252. [DOI] [PMC free article] [PubMed] [Google Scholar]
189.Cheung C, Tu S, Feng Y, Wan C, Ai H, Chen Z. Mitochondrial quality control dysfunction in osteoarthritis: Mechanisms, therapeutic strategies and future prospects. Arch Gerontol Geriatr 2024;125:105522. doi: 10.1016/j.archger.2024.105522. [DOI] [PubMed] [Google Scholar]
190.Pietrangelo D, Lopa C, Litterio M, Cotugno M, Rubattu S, Lombardi A. Metabolic disturbances involved in cardiovascular diseases: The role of mitochondrial dysfunction, altered bioenergetics and oxidative stress. Int J Mol Sci 2025;26:6791. doi: 10.3390/ijms26146791. [DOI] [PMC free article] [PubMed] [Google Scholar]
191.Wang Y, Liu HH, Cao YT, Zhang LL, Huang F, Yi C. The role of mitochondrial dynamics and mitophagy in carcinogenesis, metastasis and therapy. Front Cell Dev Biol 2020;8:413. doi: 10.3389/fcell.2020.00413. [DOI] [PMC free article] [PubMed] [Google Scholar]
192.Romanello V, Sandri M. Implications of mitochondrial fusion and fission in skeletal muscle mass and health. Semin Cell Dev Biol 2023;143:46-53. doi: 10.1016/j.semcdb.2022.02.011. [DOI] [PubMed] [Google Scholar]
193.Kabra UD, Jastroch M. Mitochondrial dynamics and insulin secretion. Int J Mol Sci 2023;24:13782. doi: 10.3390/ijms241813782. [DOI] [PMC free article] [PubMed] [Google Scholar]
194.Zhang L, Wei Y, Yuan S, Sun L. Targeting mitochondrial metabolic reprogramming as a potential approach for cancer therapy. Int J Mol Sci 2023;24:4954. doi: 10.3390/ijms24054954. [DOI] [PMC free article] [PubMed] [Google Scholar]
195.Ruan P, Zheng Y, Dong Z, Wang Y, Xu Y, Chen H. Research progress in the regulation of autophagy and mitochondrial homeostasis by AMPK signaling channels (in Chinese). Chinese Critical Care Medicine 2024;36:425-429. doi: 10.3760/cma.j.cn121430-20230302-00132. [DOI] [PubMed] [Google Scholar]
196.Ahmed Selim N, Wojtovich AP. Mitochondrial membrane potential and compartmentalized signaling: Calcium, ROS, and beyond. Redox Biol 2025;86:103859. doi: 10.1016/j.redox.2025.103859. [DOI] [PMC free article] [PubMed] [Google Scholar]
197.Zhang L Qi J Zhang X Zhao X An P Luo Y, et al. The regulatory roles of mitochondrial calcium and the mitochondrial calcium uniporter in tumor cells. Int J Mol Sci 2022;23:6667. doi: 10.3390/ijms23126667. [DOI] [PMC free article] [PubMed] [Google Scholar]
198.Chen L, Liu Y, Zhang J, Song T, Wu J, Ren Z. AMPK regulates ARF1 localization to membrane contact sites to facilitate fatty acid transfer between lipid droplets and mitochondria. Cell Death Dis 2025;16:623. doi: 10.1038/s41419-025-07957-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
199.Li YE, Sowers JR, Hetz C, Ren J. Cell death regulation by MAMs: From molecular mechanisms to therapeutic implications in cardiovascular diseases. Cell Death Dis 2022;13:504. doi: 10.1038/s41419-022-04942-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
200.Favorit V, Hood WR, Kavazis AN, Skibiel AL. Graduate student literature review: Mitochondrial adaptations across lactation and their molecular regulation in dairy cattle. J Dairy Sci 2021;104:10415-10425. doi: 10.3168/jds.2021-20138. [DOI] [PMC free article] [PubMed] [Google Scholar]
201.Song H Zhang X Wang J Wu Y Xiong T Shen J, et al. The regulatory role of adipocyte mitochondrial homeostasis in metabolism-related diseases. Front Physiol 2023;14:1261204. doi: 10.3389/fphys.2023.1261204. [DOI] [PMC free article] [PubMed] [Google Scholar]
202.Yu LP Li YQ Li YJ Zi L Tao YX Hao JJ, et al. In vivo identification of the pharmacodynamic ingredients of polygonum cuspidatum for remedying the mitochondria to alleviate metabolic dysfunction-associated fatty liver disease. Biomed Pharmacother 2022;156:113849. doi: 10.1016/j.biopha.2022.113849. [DOI] [PubMed] [Google Scholar]
203.Shen X, Sun P, Zhang H, Yang H. Mitochondrial quality control in the brain: The physiological and pathological roles. Front Neurosci 2022;16:1075141. doi: 10.3389/fnins.2022.1075141. [DOI] [PMC free article] [PubMed] [Google Scholar]
204.Lei X Xu Z Huang L Huang Y Tu S Xu L, et al. The potential influence of melatonin on mitochondrial quality control: A review. Front Pharmacol 2023;14:1332567. doi: 10.3389/fphar.2023.1332567. [DOI] [PMC free article] [PubMed] [Google Scholar]
205.Stojakovic A Chang SY Nesbitt J Pichurin NP Ostroot MA Aikawa T, et al. Partial inhibition of mitochondrial complex I reduces tau pathology and improves energy homeostasis and synaptic function in 3xTg-AD mice. J Alzheimers Dis 2021;79:335-353. doi: 10.3233/JAD-201015. [DOI] [PMC free article] [PubMed] [Google Scholar]
206.Liu Y Fu T Li G Li B Luo G Li N, et al. Mitochondrial transfer between cell crosstalk-An emerging role in mitochondrial quality control. Ageing Res Rev 2023;91:102038. doi: 10.1016/j.arr.2023.102038. [DOI] [PubMed] [Google Scholar]
207.Zhong Y Liu J Sun D Guo T Yao Y Xia X, et al. Dioscin relieves diabetic nephropathy via suppressing oxidative stress and apoptosis, and improving mitochondrial quality and quantity control. Food Funct 2022;13:3660-3673. doi: 10.1039/d1fo02733f. [DOI] [PubMed] [Google Scholar]
208.Ma X Liu Y Ding B Liu Y Zhang Y Wang Y, et al. Blueberry anthocyanins ameliorate arsenic-induced cognitive impairment in rats: Mitigating mitochondrial damage and dysregulation. Phytomedicine 2025;145:157062. doi: 10.1016/j.phymed.2025.157062. [DOI] [PubMed] [Google Scholar]
209.Tang H, Zheng Z, Wang H, Wang L, Zhao G, Wang P. Vitamin K2 modulates mitochondrial dysfunction induced by 6-hydroxydopamine in SH-SY5Y cells via mitochondrial quality-control loop. Nutrients 2022;14:1504. doi: 10.3390/nu14071504. [DOI] [PMC free article] [PubMed] [Google Scholar]
210.Ning X Tang J Li X Wang J Zhai F Jiang C, et al. Dexmedetomidine ameliorates hepatic ischemia reperfusion injury via modulating SIRT3 mediated mitochondrial quality control. Sci Rep 2025;15:5630. doi: 10.1038/s41598-025-90069-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
211.Vandvali F, Kia HD, Najafi A, Rafieian-Naeini HR, Kim WK. Improving rooster semen cryopreservation with telmisartan-enhanced extender. Poult Sci 2025;104:104694. doi: 10.1016/j.psj.2024.104694. [DOI] [PMC free article] [PubMed] [Google Scholar]
212.Vandvali F, Kia HD, Ebrahimi M, Moghaddam G, Najafi A. Impact of losartan-supplemented extender on enhancing rooster sperm quality post-freezing and thawing. Poult Sci 2025;104:105179. doi: 10.1016/j.psj.2025.105179. [DOI] [PMC free article] [PubMed] [Google Scholar]
213.Kuzelova L Svoradova A Balazi A Vasicek J Langraf V Kolesarova A, et al. Enhancing of rabbit sperm cryopreservation with antioxidants mito-tempo and berberine. Antioxidants (Basel) 2024;13:1360. doi: 10.3390/antiox13111360. [DOI] [PMC free article] [PubMed] [Google Scholar]
214.He L, Liu F, Li J. Mitochondrial sirtuins and doxorubicin-induced cardiotoxicity. Cardiovasc Toxicol 2021;21:179-191. doi: 10.1007/s12012-020-09626-x. [DOI] [PubMed] [Google Scholar]
215.Zhang P Lu H Wu Y Lu D Li C Yang X, et al. COX5A alleviates doxorubicin-induced cardiotoxicity by suppressing oxidative stress, mitochondrial dysfunction and cardiomyocyte apoptosis. Int J Mol Sci 2023;24:10400. doi: 10.3390/ijms241210400. [DOI] [PMC free article] [PubMed] [Google Scholar]
216.Luo H Jin M Hu H Ying Q Hu P Sheng W, et al. SIRT4 protects muller glial cells against apoptosis by mediating mitochondrial dynamics and oxidative stress. Mol Neurobiol 2025;62:6683-6702. doi: 10.1007/s12035-024-04349-4. [DOI] [PubMed] [Google Scholar]
217.Chen W Zhuang A Liu C He Y Kaixin L Jiang T, et al. Mitochondrial enzyme HIBADH protects against calcium oxalate nephrolithiasis by modulating oxidative stress and apoptosis. Arch Biochem Biophys 2025;770:110452. doi: 10.1016/j.abb.2025.110452. [DOI] [PubMed] [Google Scholar]
218.Zhang X Zhang D Li H Liu Z Yang Y Li J, et al. Melatonin-mediated suppression of mtROS-JNK-FOXO1 pathway alleviates hypoxia-induced apoptosis in porcine granulosa cells. Antioxidants (Basel) 2023;12:1881. doi: 10.3390/antiox12101881. [DOI] [PMC free article] [PubMed] [Google Scholar]
219.Yang Y Zhou Y Zhao X Dang R Fan P Feng F, et al. The effect of TSPO transmembrane transport-mediated paeonol mitochondrial antioxidant on dexamethasone-induced mitochondrial abnormalities, oxidative stress damage, and apoptosis in SV40-MES-13 cells. Exp Cell Res 2025;450:114674. doi: 10.1016/j.yexcr.2025.114674. [DOI] [PubMed] [Google Scholar]
220.Peng X Wang K Zhang C Bao JP Vlf C Gao JW, et al. The mitochondrial antioxidant SS-31 attenuated lipopolysaccharide-induced apoptosis and pyroptosis of nucleus pulposus cells via scavenging mitochondrial ROS and maintaining the stability of mitochondrial dynamics. Free Radic Res 2021;55:1080-1093. doi: 10.1080/10715762.2021.2018426. [DOI] [PubMed] [Google Scholar]
221.Yu JX, Lin M, Zhang WX, Lao FX, Huang HC. Astaxanthin prevents oxidative damage and cell apoptosis under oxidative stress involving the restoration of mitochondrial function. Cell Biochem Funct 2024;42:e70027. doi: 10.1002/cbf.70027. [DOI] [PubMed] [Google Scholar]
222.Elmorsy EM Al Doghaither HA Al-Ghafari AB Ebrahim NA Mohamed ME Ibrahim SF, et al. Hyperoside protects human osteoblasts from phthalate-induced mitochondrial dysfunction, oxidative stress, and apoptosis. Toxicol Appl Pharmacol 2025;503:117491. doi: 10.1016/j.taap.2025.117491. [DOI] [PubMed] [Google Scholar]
223.Yao ZK Jean YH Lin SC Lai YC Chen NF Tseng CC, et al. Manoalide induces intrinsic apoptosis by oxidative stress and mitochondrial dysfunction in human osteosarcoma cells. Antioxidants (Basel) 2023;12:1422. doi: 10.3390/antiox12071422. [DOI] [PMC free article] [PubMed] [Google Scholar]
224.Arun B, Gopinath P, Jha A, Tripathi N, Dastager SG, Hasan SK. Nigericin-induced apoptosis in acute myeloid leukemia via mitochondrial dysfunction and oxidative stress. Oncol Res 2025;33:2161-2174. doi: 10.32604/or.2025.062951. [DOI] [PMC free article] [PubMed] [Google Scholar]
225.Yan X, Wang B, Hu Y, Wang S, Zhang X. Abnormal mitochondrial quality control in neurodegenerative diseases. Front Cell Neurosci 2020;14:138. doi: 10.3389/fncel.2020.00138. [DOI] [PMC free article] [PubMed] [Google Scholar]
226.Liu T Sun W Guo S Yuan Z Zhu M Lu J, et al. Role of mitochondrial quality control in neurodegenerative disease progression. Front Cell Neurosci 2025;19:1588645. doi: 10.3389/fncel.2025.1588645. [DOI] [PMC free article] [PubMed] [Google Scholar]
227.Luo JS Zhai WH Ding LL Zhang XJ Han J Ning JQ, et al. MAMs and mitochondrial quality control: Overview and their role in Alzheimer’s disease. Neurochem Res 2024;49:2682-2698. doi: 10.1007/s11064-024-04205-w. [DOI] [PubMed] [Google Scholar]
228.McGill Percy KC, Liu Z, Qi X. Mitochondrial dysfunction in Alzheimer’s disease: Guiding the path to targeted therapies. Neurotherapeutics 2025;22:e00525. doi: 10.1016/j.neurot.2025.e00525. [DOI] [PMC free article] [PubMed] [Google Scholar]
229.Tang Y, Huang Y, Wan Z, Zhou B, Wu Z. Mitochondrial quality control links two seemingly unrelated neurodegenerative diseases. Autophagy 2022;18:2495-2497. doi: 10.1080/15548627.2022.2094605. [DOI] [PMC free article] [PubMed] [Google Scholar]
230.Pareek G. AAA+ proteases: The first line of defense against mitochondrial damage. PeerJ 2022;10:e14350. doi: 10.7717/peerj.14350. [DOI] [PMC free article] [PubMed] [Google Scholar]
231.Ragupathy H, Vukku M, Barodia SK. Cell-type-specific mitochondrial quality control in the brain: A plausible mechanism of neurodegeneration. Int J Mol Sci 2023;24:14421. doi: 10.3390/ijms241914421. [DOI] [PMC free article] [PubMed] [Google Scholar]
232.Hu D, Liu Z, Qi X. Mitochondrial quality control strategies: Potential therapeutic targets for neurodegenerative diseases? Front Neurosci 2021;15:746873. doi: 10.3389/fnins.2021.746873. [DOI] [PMC free article] [PubMed] [Google Scholar]
233.Dominiak A, Gawinek E, Banaszek AA, Wilkaniec A. Mitochondrial quality control in neurodegeneration and cancer: A common denominator, distinct therapeutic challenges. Int J Mol Sci 2025;26:8693. doi: 10.3390/ijms26178693. [DOI] [PMC free article] [PubMed] [Google Scholar]
234.Singh D. Mitochondrial dysfunction in neurodegenerative disorders: Role of prototype targeted drug delivery solutions. Curr Drug Saf 2025. doi: 10.2174/0115748863375490250626163609. [DOI] [PubMed] [Google Scholar]
235.Mantle D, Hargreaves IP. Mitochondrial dysfunction and neurodegenerative disorders: Role of nutritional supplementation. Int J Mol Sci 2022;23:12603. doi: 10.3390/ijms232012603. [DOI] [PMC free article] [PubMed] [Google Scholar]
236.Ikawa M, Okazawa H, Nakamoto Y, Yoneda M. PET imaging for oxidative stress in neurodegenerative disorders associated with mitochondrial dysfunction. Antioxidants (Basel) 2020;9:861. doi: 10.3390/antiox9090861. [DOI] [PMC free article] [PubMed] [Google Scholar]
237.Prasuhn J, Kunert L, Bruggemann N. Neuroimaging methods to map in vivo changes of OXPHOS and oxidative stress in neurodegenerative disorders. Int J Mol Sci 2022;23:7263. doi: 10.3390/ijms23137263. [DOI] [PMC free article] [PubMed] [Google Scholar]
238.Granat L, Hunt RJ, Bateman JM. Mitochondrial retrograde signalling in neurological disease. Philos Trans R Soc Lond B Biol Sci 2020;375:20190415. doi: 10.1098/rstb.2019.0415. [DOI] [PMC free article] [PubMed] [Google Scholar]
239.Atici AE, Crother TR, Noval Rivas M. Mitochondrial quality control in health and cardiovascular diseases. Front Cell Dev Biol 2023;11:1290046. doi: 10.3389/fcell.2023.1290046. [DOI] [PMC free article] [PubMed] [Google Scholar]
240.Inferrera F, Marino Y, Genovese T, Cuzzocrea S, Fusco R, Di Paola R. Mitochondrial quality control: Biochemical mechanism of cardiovascular disease. Biochim Biophys Acta Mol Cell Res 2025;1872:119906. doi: 10.1016/j.bbamcr.2025.119906. [DOI] [PubMed] [Google Scholar]
241.Chang X Zhang W Zhao Z Ma C Zhang T Meng Q, et al. Regulation of mitochondrial quality control by natural drugs in the treatment of cardiovascular diseases: Potential and advantages. Front Cell Dev Biol 2020;8:616139. doi: 10.3389/fcell.2020.616139. [DOI] [PMC free article] [PubMed] [Google Scholar]
242.Oh CM, Ryu D, Cho S, Jang Y. Mitochondrial quality control in the heart: New drug targets for cardiovascular disease. Korean Circ J 2020;50:395-405. doi: 10.4070/kcj.2019.0416. [DOI] [PMC free article] [PubMed] [Google Scholar]
243.Zhang M Zhang T Zou R He K Huang R Feng J, et al. Mitochondrial quality control as a therapeutic target in cardiovascular disease: Mechanistic insights and future directions. J Transl Int Med 2025;13:211-240. doi: 10.1515/jtim-2025-0030. [DOI] [PMC free article] [PubMed] [Google Scholar]
244.Ravindran R, Gustafsson AB. Mitochondrial quality control in cardiomyocytes: Safeguarding the heart against disease and ageing. Nat Rev Cardiol 2025;22:798-813. doi: 10.1038/s41569-025-01142-1. [DOI] [PubMed] [Google Scholar]
245.Svagusa T Sikiric S Milavic M Sepac A Seiwerth S Milicic D, et al. Heart failure in patients is associated with downregulation of mitochondrial quality control genes. Eur J Clin Invest 2023;53:e14054. doi: 10.1111/eci.14054. [DOI] [PubMed] [Google Scholar]
246.Wang J, Zhou H. Mitochondrial quality control mechanisms as molecular targets in cardiac ischemia-reperfusion injury. Acta Pharm Sin B 2020;10:1866-1879. doi: 10.1016/j.apsb.2020.03.004. [DOI] [PMC free article] [PubMed] [Google Scholar]
247.Chang X, Liu R, Li R, Peng Y, Zhu P, Zhou H. Molecular mechanisms of mitochondrial quality control in ischemic cardiomyopathy. Int J Biol Sci 2023;19:426-448. doi: 10.7150/ijbs.76223. [DOI] [PMC free article] [PubMed] [Google Scholar]
248.Tan Y, Lei C, Tang H, Zhu X, Yi G. The hippo pathway orchestrates mitochondrial quality control: A novel focus on cardiovascular diseases. DNA Cell Biol 2020;39:1494-1505. doi: 10.1089/dna.2019.5348. [DOI] [PubMed] [Google Scholar]
249.Ruan L, Wang Y, Zhang X, Tomaszewski A, McNamara JT, Li R. Mitochondria-associated proteostasis. Annu Rev Biophys 2020;49:41-67. doi: 10.1146/annurev-biophys-121219-081604. [DOI] [PubMed] [Google Scholar]
250.Kanwar YS, Sun L, Xie P, Liu FY, Chen S. A glimpse of various pathogenetic mechanisms of diabetic nephropathy. Annu Rev Pathol 2011;6:395-423. doi: 10.1146/annurev.pathol.4.110807.092150. [DOI] [PMC free article] [PubMed] [Google Scholar]
251.Sheng J, Li X, Lei J, Gan W, Song J. Mitochondrial quality control in acute kidney disease. J Nephrol 2023;36:1283-1291. doi: 10.1007/s40620-023-01582-3. [DOI] [PubMed] [Google Scholar]
252.Yang M Zhang Q Luo S Han Y Zhao H Jiang N, et al. DsbA-L alleviates tubular injury in diabetic nephropathy by activating mitophagy through maintenance of MAM integrity. Clin Sci (Lond) 2023;137:931-945. doi: 10.1042/CS20220787. [DOI] [PubMed] [Google Scholar]
253.Yang M Liu Y Luo SL Liu CB Jiang N Li CR, et al. DsbA-L ameliorates renal aging and renal fibrosis by maintaining mitochondrial homeostasis. Acta Pharmacol Sin 2024;45:777-789. doi: 10.1038/s41401-023-01216-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
254.Gao P, Yang M, Chen X, Xiong S, Liu J, Sun L. DsbA-L deficiency exacerbates mitochondrial dysfunction of tubular cells in diabetic kidney disease. Clin Sci (Lond) 2020;134:677-694. doi: 10.1042/CS20200005. [DOI] [PubMed] [Google Scholar]
255.Bhatia D, Capili A, Choi ME. Mitochondrial dysfunction in kidney injury, inflammation, and disease: Potential therapeutic approaches. Kidney Res Clin Pract 2020;39:244-258. doi: 10.23876/j.krcp.20.082. [DOI] [PMC free article] [PubMed] [Google Scholar]
256.Tan ZX, Zhu WZ. Regulatory mechanisms of mitochondrial dynamics and its emerging role in renal pathophysiology (in Chinese). Acta Physiologica Sinica 2024;76:148-160. [PubMed] [Google Scholar]
257.Zhan M, Brooks C, Liu F, Sun L, Dong Z. Mitochondrial dynamics: Regulatory mechanisms and emerging role in renal pathophysiology. Kidney Int 2013;83:568-581. doi: 10.1038/ki.2012.441. [DOI] [PMC free article] [PubMed] [Google Scholar]
258.Yang S Han Y Liu J Song P Xu X Zhao L, et al. Mitochondria: A novel therapeutic target in diabetic nephropathy. Curr Med Chem 2017;24:3185-3202. doi: 10.2174/0929867324666170509121003. [DOI] [PubMed] [Google Scholar]
259.Yang M Liu C Jiang N Liu Y Luo S Li C, et al. Mitochondrial homeostasis: A potential target for delaying renal aging. Front Pharmacol 2023;14:1191517. doi: 10.3389/fphar.2023.1191517. [DOI] [PMC free article] [PubMed] [Google Scholar]
260.Bhatia D, Choi ME. The emerging role of mitophagy in kidney diseases. J Life Sci (Westlake Village) 2019;1:13-22. doi: 10.36069/jols/20191203. [DOI] [PMC free article] [PubMed] [Google Scholar]
261.Fan X, Wu L, Wang F, Liu D, Cen X, Xia H. Mitophagy regulates kidney diseases. Kidney Dis (Basel) 2024;10:573-587. doi: 10.1159/000541486. [DOI] [PMC free article] [PubMed] [Google Scholar]
262.Wang Y, Cai J, Tang C, Dong Z. Mitophagy in acute kidney injury and kidney repair. Cells 2020;9:338. doi: 10.3390/cells9020338. [DOI] [PMC free article] [PubMed] [Google Scholar]
263.Sabry MM Ahmed MM Maksoud OMA Rashed L Morcos MA El-Maaty AA, et al. Carnitine, apelin and resveratrol regulate mitochondrial quality control (QC) related proteins and ameliorate acute kidney injury: Role of hydrogen peroxide. Arch Physiol Biochem 2022;128:1391-1400. doi: 10.1080/13813455.2020.1773504. [DOI] [PubMed] [Google Scholar]
264.Hurtado K, Scholpa NE, Schnellmann JG, Schnellmann RG. Serotonin regulation of mitochondria in kidney diseases. Pharmacol Res 2024;203:107154. doi: 10.1016/j.phrs.2024.107154. [DOI] [PMC free article] [PubMed] [Google Scholar]
265.Srivastava A, Tomar B, Sharma D, Rath SK. Mitochondrial dysfunction and oxidative stress: Role in chronic kidney disease. Life Sci 2023;319:121432. doi: 10.1016/j.lfs.2023.121432. [DOI] [PubMed] [Google Scholar]
266.Sang XY Xiao JJ Liu Q Zhu R Dai JJ Zhang C, et al. Regulators of calcineurin 1 deficiency attenuates tubulointerstitial fibrosis through improving mitochondrial fitness. FASEB J 2020;34. doi: 10.1096/fj.202000781RRR. [DOI] [PubMed] [Google Scholar]
267.Yang X Feng J Liang W Zhu Z Chen Z Hu J, et al. Roles of SIRT6 in kidney disease: A novel therapeutic target. Cell Mol Life Sci 2021;79:53. doi: 10.1007/s00018-021-04061-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
268.Xu L Wang J Yu H Mei H He P Wang M, et al. GLIS1 alleviates cell senescence and renal fibrosis through PGC1-alpha mediated mitochondrial quality control in kidney aging. Free Radic Biol Med 2023;209:171-184. doi: 10.1016/j.freeradbiomed.2023.09.037. [DOI] [PubMed] [Google Scholar]
269.Zhang M Tong Z Wang Y Fu W Meng Y Huang J, et al. Relationship between ferroptosis and mitophagy in renal fibrosis: A systematic review. J Drug Target 2023;31:858-866. doi: 10.1080/1061186X.2023.2250574. [DOI] [PubMed] [Google Scholar]
270.Xiao L Xu X Zhang F Wang M Xu Y Tang D, et al. The mitochondria-targeted antioxidant MitoQ ameliorated tubular injury mediated by mitophagy in diabetic kidney disease via Nrf2/PINK1. Redox Biol 2017;11:297-311. doi: 10.1016/j.redox.2016.12.022. [DOI] [PMC free article] [PubMed] [Google Scholar]
271.Liu S, Yuan Y, Xue Y, Xing C, Zhang B. Podocyte injury in diabetic kidney disease: A focus on mitochondrial dysfunction. Front Cell Dev Biol 2022;10:832887. doi: 10.3389/fcell.2022.832887. [DOI] [PMC free article] [PubMed] [Google Scholar]
272.Dai W, Lu H, Chen Y, Yang D, Sun L, He L. The loss of mitochondrial quality control in diabetic kidney disease. Front Cell Dev Biol 2021;9:706832. doi: 10.3389/fcell.2021.706832. [DOI] [PMC free article] [PubMed] [Google Scholar]
273.Bhatia D, Choi ME. Autophagy and mitophagy: Physiological implications in kidney inflammation and diseases. Am J Physiol Renal Physiol 2023;325:F1-F21. doi: 10.1152/ajprenal.00012.2023. [DOI] [PMC free article] [PubMed] [Google Scholar]
274.Han Y Xu X Tang C Gao P Chen X Xiong X, et al. Reactive oxygen species promote tubular injury in diabetic nephropathy: The role of the mitochondrial ros-txnip-nlrp3 biological axis. Redox Biol 2018;16:32-46. doi: 10.1016/j.redox.2018.02.013. [DOI] [PMC free article] [PubMed] [Google Scholar]
275.Sun L Xiao L Nie J Liu FY Ling GH Zhu XJ, et al. p66Shc mediates high-glucose and angiotensin II-induced oxidative stress renal tubular injury via mitochondrial-dependent apoptotic pathway. Am J Physiol Renal Physiol 2010;299:F1014-F1025. doi: 10.1152/ajprenal.00414.2010. [DOI] [PMC free article] [PubMed] [Google Scholar]
276.Prem PN, Swaminathan H, Kurian GA. The temporal relationship between mitochondrial quality and renal tissue recovery following ischemia-reperfusion injury. Heliyon 2025;11:e41634. doi: 10.1016/j.heliyon.2025.e41634. [DOI] [PMC free article] [PubMed] [Google Scholar]
277.Zanini G Micheloni G Sinigaglia G Selleri V Mattioli AV Nasi M, et al. Modulation of Lonp1 activity by small compounds. Biomolecules 2025;15:553. doi: 10.3390/biom15040553. [DOI] [PMC free article] [PubMed] [Google Scholar]
278.Liu Y Zhang L Zhang S Liu J Li X Yang K, et al. ATF5 regulates tubulointerstitial injury in diabetic kidney disease via mitochondrial unfolded protein response. Mol Med 2023;29:57. doi: 10.1186/s10020-023-00651-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
279.Yu Y Chen M Guo Q Shen L Liu X Pan J, et al. Human umbilical cord mesenchymal stem cell exosome-derived miR-874-3p targeting RIPK1/PGAM5 attenuates kidney tubular epithelial cell damage. Cell Mol Biol Lett 2023;28:12. doi: 10.1186/s11658-023-00425-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
280.Lee TW, Bae E, Kim JH, Jung MH, Park DJ. Zileuton attenuates acute kidney injury in glycerol-induced rhabdomyolysis by regulating myeloid-derived suppressor cells in mice. Int J Mol Sci 2025;26:8353. doi: 10.3390/ijms26178353. [DOI] [PMC free article] [PubMed] [Google Scholar]
281.Luo S Yang M Zhao H Han Y Liu Y Xiong X, et al. Mitochondrial DNA-dependent inflammation in kidney diseases. Int Immunopharmacol 2022;107:108637. doi: 10.1016/j.intimp.2022.108637. [DOI] [PubMed] [Google Scholar]
282.Zhang L Xu Z Jing J Chai G Xie G Ru Y, et al. Age-dependent accumulation of mitochondrial tRNA mutations in mouse kidneys linked to mitochondrial kidney diseases. Nat Aging 2025;5:1317-1339. doi: 10.1038/s43587-025-00909-y. [DOI] [PubMed] [Google Scholar]
283.Duan T Sun L Xi Y Li C Zhao Q Xu L, et al. Mito-tempo ameliorates tubular injury of diabetic nephropathy via inhibiting mt-dsRNA release and PKR/eIF2alpha pathway activation. Free Radic Biol Med 2025;237:147-159. doi: 10.1016/j.freeradbiomed.2025.05.431. [DOI] [PubMed] [Google Scholar]
284.Duan T Sun L Ding K Zhao Q Xu L Liu C, et al. Mitochondrial RNA metabolism, a potential therapeutic target for mitochondria-related diseases. Chin Med J 2025;138:808-818. doi: 10.1097/CM9.0000000000003516. [DOI] [PMC free article] [PubMed] [Google Scholar]
285.Tang C, Cai J, Yin XM, Weinberg JM, Venkatachalam MA, Dong Z. Mitochondrial quality control in kidney injury and repair. Nat Rev Nephrol 2021;17:299-318. doi: 10.1038/s41581-020-00369-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
286.Ito M, Gurumani MZ, Merscher S, Fornoni A. Glucose- and non-glucose-induced mitochondrial dysfunction in diabetic kidney disease. Biomolecules 2022;12:351. doi: 10.3390/biom12030351. [DOI] [PMC free article] [PubMed] [Google Scholar]
287.Shin S, Kim J, Lee JY, Kim J, Oh CM. Mitochondrial quality control: Its role in metabolic dysfunction-associated steatotic liver disease (MASLD). J Obes Metab Syndr 2023;32:289-302. doi: 10.7570/jomes23054. [DOI] [PMC free article] [PubMed] [Google Scholar]
288.Cioffi F Giacco A Petito G de Matteis R Senese R Lombardi A, et al. Altered mitochondrial quality control in rats with metabolic dysfunction-associated fatty liver disease (MAFLD) induced by high-fat feeding. Genes (Basel) 2022;13:315. doi: 10.3390/genes13020315. [DOI] [PMC free article] [PubMed] [Google Scholar]
289.Giacco A Petito G Silvestri E Scopigno N Vigliotti M Mercurio G, et al. Comparative effects of 3,5-diiodo-L-thyronine and 3,5,3′-triiodo-L-thyronine on mitochondrial damage and cGAS/STING-driven inflammation in liver of hypothyroid rats. Front Endocrinol (Lausanne) 2024;15:1432819. doi: 10.3389/fendo.2024.1432819. [DOI] [PMC free article] [PubMed] [Google Scholar]
290.Cai C Wu F He J Zhang Y Shi N Peng X, et al. Mitochondrial quality control in diabetic cardiomyopathy: From molecular mechanisms to therapeutic strategies. Int J Biol Sci 2022;18:5276-5290. doi: 10.7150/ijbs.75402. [DOI] [PMC free article] [PubMed] [Google Scholar]
291.Zhou Y Suo W Zhang X Liang J Zhao W Wang Y, et al. Targeting mitochondrial quality control for diabetic cardiomyopathy: Therapeutic potential of hypoglycemic drugs. Biomed Pharmacother 2023;168:115669. doi: 10.1016/j.biopha.2023.115669. [DOI] [PubMed] [Google Scholar]
292.Li Q, Shang J, Inagi R. Control of mitochondrial quality: A promising target for diabetic kidney disease treatment. Kidney Int Rep 2025;10:994-1010. doi: 10.1016/j.ekir.2024.12.029. [DOI] [PMC free article] [PubMed] [Google Scholar]
293.Liu P, Chen Y, Xiao J, Zhu W, Yan X, Chen M. Protective effect of natural products in the metabolic-associated kidney diseases via regulating mitochondrial dysfunction. Front Pharmacol 2022;13:1093397. doi: 10.3389/fphar.2022.1093397. [DOI] [PMC free article] [PubMed] [Google Scholar]
294.Prasun P. Mitochondrial dysfunction in metabolic syndrome. Biochim Biophys Acta Mol Basis Dis 2020;1866:165838. doi: 10.1016/j.bbadis.2020.165838. [DOI] [PubMed] [Google Scholar]
295.Todosenko N Khaziakhmatova O Malashchenko V Yurova K Bograya M Beletskaya M, et al. Mitochondrial dysfunction associated with mtDNA in metabolic syndrome and obesity. Int J Mol Sci 2023;24:12012. doi: 10.3390/ijms241512012. [DOI] [PMC free article] [PubMed] [Google Scholar]
296.Zhang Q Ren J Wang F Pan M Cui L Li M, et al. Mitochondrial and glucose metabolic dysfunctions in granulosa cells induce impaired oocytes of polycystic ovary syndrome through Sirtuin 3. Free Radic Biol Med 2022;187:1-16. doi: 10.1016/j.freeradbiomed.2022.05.010. [DOI] [PubMed] [Google Scholar]
297.Zeng X, Huang Q, Long SL, Zhong Q, Mo Z. Mitochondrial dysfunction in polycystic ovary syndrome. DNA Cell Biol 2020;39:1401-1409. doi: 10.1089/dna.2019.5172. [DOI] [PubMed] [Google Scholar]
298.Moisoi N. Mitochondrial proteases modulate mitochondrial stress signalling and cellular homeostasis in health and disease. Biochimie 2024;226:165-179. doi: 10.1016/j.biochi.2024.06.005. [DOI] [PubMed] [Google Scholar]
299.Karbowski M, Oshima Y, Verhoeven N. Mitochondrial proteotoxicity: Implications and ubiquitin-dependent quality control mechanisms. Cell Mol Life Sci 2022;79:574. doi: 10.1007/s00018-022-04604-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
300.Zhou S Xiong X Hou J Duan Q Zheng Y Jiang T, et al. NAD+-boosters improve mitochondria quality control in Parkinson’s disease models via mitochondrial UPR. Adv Sci (Weinh) 2025;12:e08503. doi: 10.1002/advs.202408503. [DOI] [PMC free article] [PubMed] [Google Scholar]
301.Fallahi F Mostafavinia A Sharifi Z Mohaghegh Shalmani L Amini A Ahmadi H, et al. Effects of photobiomodulation on mitochondrial function in diabetic adipose-derived stem cells in vitro. Spectrochim Acta A Mol Biomol Spectrosc 2023;285:121835. doi: 10.1016/j.saa.2022.121835. [DOI] [PubMed] [Google Scholar]
302.Chen Q, Zhang Q, Amrouche AT, Huang W, Lu B. Asperuloside, the bioactive compound in the edible Eucommia ulmoides male flower, delays muscle aging by daf-16 mediated improvement in mitochondrial dysfunction. Food Funct 2023;14:5562-5575. doi: 10.1039/d3fo01024d. [DOI] [PubMed] [Google Scholar]
303.Yeon MH, Seo E, Lee JH, Jun HS. Bavachin and corylifol a improve muscle atrophy by enhancing mitochondria quality control in type 2 diabetic mice. Antioxidants (Basel) 2023;12:137. doi: 10.3390/antiox12010137. [DOI] [PMC free article] [PubMed] [Google Scholar]
304.Inigo JR, Chandra D. The mitochondrial unfolded protein response (UPR(mt)): Shielding against toxicity to mitochondria in cancer. J Hematol Oncol 2022;15:98. doi: 10.1186/s13045-022-01317-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
305.Liu Y Wang H Zhang S Peng N Hai S Zhao H, et al. The role of mitochondrial biogenesis, mitochondrial dynamics and mitophagy in gastrointestinal tumors. Cancer Cell Int 2025;25:46. doi: 10.1186/s12935-025-03685-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
306.Han P, Ren X, Qu X, Meng Y. The regulatory mechanisms of dynamin-related protein 1 in tumor development and therapy. Cancer Biother Radiopharm 2021;36:10-17. doi: 10.1089/cbr.2020.3791. [DOI] [PubMed] [Google Scholar]
307.Gallo Cantafio ME, Torcasio R, Viglietto G, Amodio N. Non-coding RNA-dependent regulation of mitochondrial dynamics in cancer pathophysiology. Noncoding RNA 2023;9:16. doi: 10.3390/ncrna9010016. [DOI] [PMC free article] [PubMed] [Google Scholar]
308.Sano H Futamura M Gaowa S Kamino H Nakamura Y Yamaguchi K, et al. p53/Mieap-regulated mitochondrial quality control plays an important role as a tumor suppressor in gastric and esophageal cancers. Biochem Biophys Res Commun 2020;529:582-589. doi: 10.1016/j.bbrc.2020.05.168. [DOI] [PubMed] [Google Scholar]
309.Nouri K, Feng Y, Schimmer AD. Mitochondrial ClpP serine protease-biological function and emerging target for cancer therapy. Cell Death Dis 2020;11:841. doi: 10.1038/s41419-020-03062-z. [DOI] [PMC free article] [PubMed] [Google Scholar]
310.Gagliardi S Mitruccio M Di Corato R Romano R Aloisi A Rinaldi R, et al. Defects of mitochondria-lysosomes communication induce secretion of mitochondria-derived vesicles and drive chemoresistance in ovarian cancer cells. Cell Commun Signal 2024;22:165. doi: 10.1186/s12964-024-01507-y. [DOI] [PMC free article] [PubMed] [Google Scholar]
311.Peng X Gao Y Liu J Shi X Li W Ma Y, et al. Mitochondria-derived vesicles: A promising and potential target for tumour therapy. Clin Transl Med 2025;15:e70320. doi: 10.1002/ctm2.70320. [DOI] [PMC free article] [PubMed] [Google Scholar]
312.Wang Q Chai D Sobhani N Sun N Neeli P Zheng J, et al. C1QBP regulates mitochondrial plasticity to impact tumor progression and antitumor immune response. Front Physiol 2022;13:1012112. doi: 10.3389/fphys.2022.1012112. [DOI] [PMC free article] [PubMed] [Google Scholar]
313.Deng X Wang Q Cheng M Chen Y Yan X Guo R, et al. Pyruvate dehydrogenase kinase 1 interferes with glucose metabolism reprogramming and mitochondrial quality control to aggravate stress damage in cancer. J Cancer 2020;11:962-973. doi: 10.7150/jca.34330. [DOI] [PMC free article] [PubMed] [Google Scholar]
314.Sandoval-Acuna C Torrealba N Tomkova V Jadhav SB Blazkova K Merta L, et al. Targeting mitochondrial iron metabolism suppresses tumor growth and metastasis by inducing mitochondrial dysfunction and mitophagy. Cancer Res 2021;81:2289-2303. doi: 10.1158/0008-5472.CAN-20-1628. [DOI] [PubMed] [Google Scholar]
315.Ma Z, Han H, Zhao Y. Mitochondrial dysfunction-targeted nanosystems for precise tumor therapeutics. Biomaterials 2023;293:121947. doi: 10.1016/j.biomaterials.2022.121947. [DOI] [PubMed] [Google Scholar]
316.Xia Y, Gao B, Zhang X. Targeting mitochondrial quality control of T cells: Regulating the immune response in HCC. Front Oncol 2022;12:993437. doi: 10.3389/fonc.2022.993437. [DOI] [PMC free article] [PubMed] [Google Scholar]
317.Greier MDC Runge A Dudas J Hartl R Santer M Dejaco D, et al. Cytotoxic response of tumor-infiltrating lymphocytes of head and neck cancer slice cultures under mitochondrial dysfunction. Front Oncol 2024;14:1364577. doi: 10.3389/fonc.2024.1364577. [DOI] [PMC free article] [PubMed] [Google Scholar]
318.Pei W Dai L Li M Cao S Xiao Y Yang Y, et al. Targeting mitochondrial quality control for the treatment of triple-negative breast cancer: From molecular mechanisms to precision therapy. Biomolecules 2025;15:970. doi: 10.3390/biom15070970. [DOI] [PMC free article] [PubMed] [Google Scholar]
319.Fang X, Wu H, Wei J, Miao R, Zhang Y, Tian J. Research progress on the pharmacological effects of berberine targeting mitochondria. Front Endocrinol (Lausanne) 2022;13:982145. doi: 10.3389/fendo.2022.982145. [DOI] [PMC free article] [PubMed] [Google Scholar]
320.Gupta N, Curcic M, Srivastava SK. Proguanil suppresses breast tumor growth in vitro and in vivo by inducing apoptosis via mitochondrial dysfunction. Cancers (Basel) 2024;16:872. doi: 10.3390/cancers16050872. [DOI] [PMC free article] [PubMed] [Google Scholar]
321.Shi C Huang H Zhou X Zhang Z Ma H Yao Q, et al. Reversing multidrug resistance by inducing mitochondrial dysfunction for enhanced chemo-photodynamic therapy in tumor. ACS Appl Mater Interfaces 2021;13:45259-45268. doi: 10.1021/acsami.1c12725. [DOI] [PubMed] [Google Scholar]
322.Wei T Chen L Shi P Wang C Peng Y Yang J, et al. Platinum (IV) drugs with cannabidiol inducing mitochondrial dysfunction and synergistically enhancing anti-tumor effects. J Inorg Biochem 2024;254:112515. doi: 10.1016/j.jinorgbio.2024.112515. [DOI] [PubMed] [Google Scholar]
323.Marzetti E Coelho-Junior HJ Calvani R Girolimetti G Di Corato R Ciciarello F, et al. Mitochondria-derived vesicles and inflammatory profiles of adults with long COVID supplemented with red beetroot juice: Secondary analysis of a randomized controlled trial. Int J Mol Sci 2025;26:1224. doi: 10.3390/ijms26031224. [DOI] [PMC free article] [PubMed] [Google Scholar]
324.Xu W Dong L Dai J Zhong L Ouyang X Li J, et al. The interconnective role of the UPS and autophagy in the quality control of cancer mitochondria. Cell Mol Life Sci 2025;82:42. doi: 10.1007/s00018-024-05556-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
325.Pickrell AM, Youle RJ. The roles of PINK1, parkin, and mitochondrial fidelity in Parkinson’s disease. Neuron 2015;85:257-273. doi: 10.1016/j.neuron.2014.12.007. [DOI] [PMC free article] [PubMed] [Google Scholar]
326.Joshi AU, Saw NL, Vogel H, Cunnigham AD, Shamloo M, Mochly-Rosen D. Inhibition of Drp1/Fis1 interaction slows progression of amyotrophic lateral sclerosis. EMBO Mol Med 2018;10:e8166. doi: 10.15252/emmm.201708166. [DOI] [PMC free article] [PubMed] [Google Scholar]
327.Qiao C, Hu XQ, Xu SH, Yao MF, Liu JP, Cao L. Targeting NME3 to restore mitochondrial fission-fusion balance defines a novel disease-modifying strategy for Parkinson’s disease. CNS Neurosci Ther 2026;32:e70822. doi: 10.1002/cns.70822. [DOI] [PMC free article] [PubMed] [Google Scholar]
328.Ma J Yang Y Zang C Chen Q Jiang Y Dong Y, et al. Inhibiting mitochondrial excessive fission alleviates the neuronal damage in Parkinson’s disease via regulating PGC-1alpha mediated mitochondrial biogenesis. Exp Neurol 2025;391:115288. doi: 10.1016/j.expneurol.2025.115288. [DOI] [PubMed] [Google Scholar]
329.Chang P Xu M Zhu J Bian J Lu Y Luo Q, et al. Pharmacological inhibition of mitochondrial division attenuates simulated high-altitude exposure-induced memory impairment in mice: Involvement of inhibition of microglia-mediated synapse elimination. CNS Neurosci Ther 2025;31:e70473. doi: 10.1111/cns.70473. [DOI] [PMC free article] [PubMed] [Google Scholar]
330.Arbo BD Andre-Miral C Nasre-Nasser RG Schimith LE Santos MG Costa-Silva D, et al. Resveratrol derivatives as potential treatments for Alzheimer’s and Parkinson’s disease. Front Aging Neurosci 2020;12:103. doi: 10.3389/fnagi.2020.00103. [DOI] [PMC free article] [PubMed] [Google Scholar]
331.Saadh MJ Nazar Saeed T Fawzi Al-Hussainy A Kyada A Ballal S Kundlas M, et al. Mechanistic insights into ubiquinone Q10 in Parkinson’s disease: Mitochondrial protection, ferroptosis inhibition, and antioxidant recycling. Arch Physiol Biochem 2026;132:134-150. doi: 10.1080/13813455.2025.2541698. [DOI] [PubMed] [Google Scholar]
332.Zhang Y Liu T Li X Liu S Zhu X Ren Y, et al. Neuroprotective effects of idebenone in a zebrafish model of Parkinson’s disease via regulating autophagy, mitigating apoptosis and oxidative stress. Neuroscience 2026;599:52-64. doi: 10.1016/j.neuroscience.2026.02.016. [DOI] [PubMed] [Google Scholar]
333.Zhang Q, Zhang W, Yuan X, Peng X, Hu G. Urolithin A in central nervous system disorders: Therapeutic applications and challenges. Biomedicines 2025;13:1553. doi: 10.3390/biomedicines13071553. [DOI] [PMC free article] [PubMed] [Google Scholar]
334.Maitra S, Ham DW, Baek M, Choe YJ, Kim NC. FDA-approved PDE4 inhibitors alleviate the dominant toxicity of ALS-FTD-associated CHCHD10(S59L) in Drosophila and human cells. iScience 2026;29:114879. doi: 10.1016/j.isci.2026.114879. [DOI] [PMC free article] [PubMed] [Google Scholar]
335.Nesci S, Rubattu S. Mitochondrial permeability transition pore: The cardiovascular disease’s molecular Achilles heel. Biomedicines 2025;13:3014. doi: 10.3390/biomedicines13123014. [DOI] [PMC free article] [PubMed] [Google Scholar]
336.Lees JG Greening DW Rudd DA Cross J Rosdah AA Lai X, et al. Cardiac-targeted delivery of a novel Drp1 inhibitor for acute cardioprotection. J Mol Cell Cardiol Plus 2024;9:100085. doi: 10.1016/j.jmccpl.2024.100085. [DOI] [PMC free article] [PubMed] [Google Scholar]
337.Zhang W, Siraj S, Zhang R, Chen Q. Mitophagy receptor FUNDC1 regulates mitochondrial homeostasis and protects the heart from I/R injury. Autophagy 2017;13:1080-1081. doi: 10.1080/15548627.2017.1300224. [DOI] [PMC free article] [PubMed] [Google Scholar]
338.Fordjour PA Wang L Gao H Li L Wang Y Nyagblordzro M, et al. Targeting BNIP3 in inflammation-mediated heart failure: A novel concept in heart failure therapy. Heart Fail Rev 2016;21:489-497. doi: 10.1007/s10741-016-9557-4. [DOI] [PubMed] [Google Scholar]
339.Halestrap AP, Pasdois P. The role of the mitochondrial permeability transition pore in heart disease. Biochim Biophys Acta 2009;1787:1402-1415. doi: 10.1016/j.bbabio.2008.12.017. [DOI] [PubMed] [Google Scholar]
340.van Rinsum A, Hu L, Qi X, Keijer J, Zhang D. Mitochondria-targeted antioxidants prevent tachypacing-induced contractile dysfunction in in vitro cardiomyocyte and in vivo drosophila models of atrial fibrillation. Antioxidants (Basel) 2025;14:1444. doi: 10.3390/antiox14121444. [DOI] [PMC free article] [PubMed] [Google Scholar]
341.Li T Guo C Liu Q Jing F Zhao M Xiong H, et al. Mesenchymal stem cells inhibit mitochondrial fission by upregulating armadillo repeat containing 1, ameliorating oxidative stress in renal fibrosis. Stem Cell Res Ther 2025;16:584. doi: 10.1186/s13287-025-04706-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
342.Ma T Yu Y Luo H Zhang Z Wei M Tian C, et al. CircAASS alleviates renal injury and fibrosis by regulating mitochondrial homeostasis in tubular epithelial cells. Autophagy 2026;22:182-206. doi: 10.1080/15548627.2025.2581212. [DOI] [PMC free article] [PubMed] [Google Scholar]
343.Birk AV Liu S Soong Y Mills W Singh P Warren JD, et al. The mitochondrial-targeted compound SS-31 re-energizes ischemic mitochondria by interacting with cardiolipin. J Am Soc Nephrol 2013;24:1250-1261. doi: 10.1681/ASN.2012121216. [DOI] [PMC free article] [PubMed] [Google Scholar]
344.Li L, Hu F. Mitophagy in tumor: Foe or friend? Endokrynol Pol 2023;74:511-519. doi: 10.5603/ep.95652. [DOI] [PubMed] [Google Scholar]
345.Alam M, Ali S, Mohammad T, Hasan GM, Yadav DK, Hassan MI. B Cell lymphoma 2: A potential therapeutic target for cancer therapy. Int J Mol Sci 2021;22:10442. doi: 10.3390/ijms221910442. [DOI] [PMC free article] [PubMed] [Google Scholar]
346.Molina JR Sun Y Protopopova M Gera S Bandi M Bristow C, et al. An inhibitor of oxidative phosphorylation exploits cancer vulnerability. Nat Med 2018;24:1036-1046. doi: 10.1038/s41591-018-0052-4. [DOI] [PubMed] [Google Scholar]
347.Low LE Kong CK Yap WH Siva SP Gan SH Siew WS, et al. Hydroxychloroquine: Key therapeutic advances and emerging nanotechnological landscape for cancer mitigation. Chem Biol Interact 2023;386:110750. doi: 10.1016/j.cbi.2023.110750. [DOI] [PubMed] [Google Scholar]
348.Davids MS, Letai A. ABT-199: Taking dead aim at BCL-2. Cancer Cell 2013;23:139-141. doi: 10.1016/j.ccr.2013.01.018. [DOI] [PMC free article] [PubMed] [Google Scholar]
349.Mehmood T, Nasir Q, Younis I, Muanprasat C. Inhibition of mitochondrial dynamics by mitochondrial division inhibitor-1 suppresses cell migration and metastatic markers in colorectal cancer HCT116 cells. J Exp Pharmacol 2025;17:143-157. doi: 10.2147/JEP.S510578. [DOI] [PMC free article] [PubMed] [Google Scholar]
350.Khetarpal SA Li H Vitale T Rhee J Challa S Castro C, et al. Cardiac adaptation to endurance exercise training requires suppression of GDF15 via PGC-1alpha. Nat Cardiovasc Res 2025;4:1277-1294. doi: 10.1038/s44161-025-00712-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
351.Hardie DG. Sensing of energy and nutrients by AMP-activated protein kinase. Am J Clin Nutr 2011;93:891S-896S. doi: 10.3945/ajcn.110.001925. [DOI] [PubMed] [Google Scholar]
352.Su Z Guo Y Huang X Feng B Tang L Zheng G, et al. Phytochemicals: Targeting mitophagy to treat metabolic disorders. Front Cell Dev Biol 2021;9:686820. doi: 10.3389/fcell.2021.686820. [DOI] [PMC free article] [PubMed] [Google Scholar]
353.Di Francesco A Deighan AG Litichevskiy L Chen Z Luciano A Robinson L, et al. Dietary restriction impacts health and lifespan of genetically diverse mice. Nature 2024;634:684-692. doi: 10.1038/s41586-024-08026-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
354.Tulipano G. Integrated or independent actions of metformin in target tissues underlying its current use and new possible applications in the endocrine and metabolic disorder area. Int J Mol Sci 2021;22:13068. doi: 10.3390/ijms222313068. [DOI] [PMC free article] [PubMed] [Google Scholar]
355.Gao Y Wei X Wei P Lu H Zhong L Tan J, et al. MOTS-c functionally prevents metabolic disorders. Metabolites 2023;13:125. doi: 10.3390/metabo13010125. [DOI] [PMC free article] [PubMed] [Google Scholar]
356.Liu C Sun M Zhao Z Yang Y Yang Y Zhao Y, et al. Urolithin A: A multi-target therapeutic candidate derived from the gut microbiota for obesity and metabolic dysfunction. Front Endocrinol (Lausanne) 2026;17:1786776. doi: 10.3389/fendo.2026.1786776. [DOI] [PMC free article] [PubMed] [Google Scholar]
357.Li QC, Wang SQ, Cao ZZ, Zhou SH. Enhanced mitophagy in cholesteatoma epithelial cells. Otol Neurotol 2023;44:688-694. doi: 10.1097/MAO.0000000000003986. [DOI] [PubMed] [Google Scholar]
358.Pradeepkiran JA, Hindle A, Kshirsagar S, Reddy PH. Are mitophagy enhancers therapeutic targets for Alzheimer’s disease? Biomed Pharmacother 2022;149:112918. doi: 10.1016/j.biopha.2022.112918. [DOI] [PMC free article] [PubMed] [Google Scholar]
359.Dorn GW,, 2nd. Small molecules that enhance mitophagy to delay aging and neurodegeneration. J Cardiovasc Aging 2022;2:45. doi: 10.20517/jca.2022.36. [DOI] [PMC free article] [PubMed] [Google Scholar]
360.Hu S Zhang C Ni L Huang C Chen D Shi K, et al. Stabilization of HIF-1alpha alleviates osteoarthritis via enhancing mitophagy. Cell Death Dis 2020;11:481. doi: 10.1038/s41419-020-2680-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
361.Ramakrishnan RK Bajbouj K Hachim MY Mogas AK Mahboub B Olivenstein R, et al. Enhanced mitophagy in bronchial fibroblasts from severe asthmatic patients. PLoS One 2020;15:e0242695. doi: 10.1371/journal.pone.0242695. [DOI] [PMC free article] [PubMed] [Google Scholar]
362.Yang C, Xiao C, Ding Z, Zhai X, Liu J, Yu M. Canagliflozin mitigates diabetic cardiomyopathy through enhanced PINK1-parkin mitophagy. Int J Mol Sci 2024;25:7008. doi: 10.3390/ijms25137008. [DOI] [PMC free article] [PubMed] [Google Scholar]
363.Zheng C, Nguyen KK, Vishnivetskiy SA, Gurevich VV, Gurevich EV. Arrestin-3 binds parkin and enhances parkin-dependent mitophagy. J Neurochem 2025;169:e16043. doi: 10.1111/jnc.16043. [DOI] [PMC free article] [PubMed] [Google Scholar]
364.Kook S, Zhan X, Thibeault K, Ahmed MR, Gurevich VV, Gurevich EV. Mdm2 enhances ligase activity of parkin and facilitates mitophagy. Sci Rep 2020;10:5028. doi: 10.1038/s41598-020-61796-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
365.Varghese N, Werner S, Grimm A, Eckert A. Dietary mitophagy enhancer: A strategy for healthy brain aging? Antioxidants (Basel) 2020;9:932. doi: 10.3390/antiox9100932. [DOI] [PMC free article] [PubMed] [Google Scholar]
366.Zhang SQ Niu Z Anisimov A Shi F Deng S Xiao X, et al. NR1D1 Inhibition enhances autophagy and mitophagy in Alzheimer’s disease models. Aging Dis 2025. doi: 10.14336/AD.2024.1654. [DOI] [PubMed] [Google Scholar]
367.Gao LP Xiao K Wu YZ Chen DD Yang XH Shi Q, et al. Enhanced mitophagy activity in prion-infected cultured cells and prion-infected experimental mice via a Pink1/Parkin-dependent mitophagy pathway. ACS Chem Neurosci 2020;11:814-829. doi: 10.1021/acschemneuro.0c00039. [DOI] [PubMed] [Google Scholar]
368.Luo P An Y He J Xing X Zhang Q Liu X, et al. Icaritin with autophagy/mitophagy inhibitors synergistically enhances anticancer efficacy and apoptotic effects through PINK1/Parkin-mediated mitophagy in hepatocellular carcinoma. Cancer Lett 2024;587:216621. doi: 10.1016/j.canlet.2024.216621. [DOI] [PubMed] [Google Scholar]
369.Han D Su T Wang M Zhang R Xu H Chu R, et al. JAK2 inhibitor protects the septic heart through enhancing mitophagy in cardiomyocytes. Biomed Pharmacother 2024;178:117279. doi: 10.1016/j.biopha.2024.117279. [DOI] [PubMed] [Google Scholar]
370.Liu C Peng Z Li P Fu H Feng J Zhang Y, et al. LncRNA RMST suppressed GBM cell mitophagy through enhancing FUS SUMOylation. Mol Ther Nucleic Acids 2020;19:1198-1208. doi: 10.1016/j.omtn.2020.01.008. [DOI] [PMC free article] [PubMed] [Google Scholar]
371.Zhang P, Chen S, Tang H, Fang W, Chen K, Chen X. CoQ10 protects against acetaminophen-induced liver injury by enhancing mitophagy. Toxicol Appl Pharmacol 2021;410:115355. doi: 10.1016/j.taap.2020.115355. [DOI] [PubMed] [Google Scholar]
372.Li SJ Tetri LH Vijayan V Elezaby A Chiang CH Lopez I, et al. Excessive mitochondrial fission and associated extracellular mitochondria mediate cardiac dysfunction in obesity cardiomyopathy. Life Sci 2025;373:123658. doi: 10.1016/j.lfs.2025.123658. [DOI] [PMC free article] [PubMed] [Google Scholar]
373.Zhou L, Su W, Wang Y, Zhang Y, Xia Z, Lei S. FOXO1 reduces STAT3 activation and causes impaired mitochondrial quality control in diabetic cardiomyopathy. Diabetes Obes Metab 2024;26:732-744. doi: 10.1111/dom.15369. [DOI] [PubMed] [Google Scholar]
374.Chang X Zhou S Liu J Wang Y Guan X Wu Q, et al. Zishen Tongyang Huoxue decoction (TYHX) alleviates sinoatrial node cell ischemia/reperfusion injury by directing mitochondrial quality control via the VDAC1-beta-tubulin signaling axis. J Ethnopharmacol 2024;320:117371. doi: 10.1016/j.jep.2023.117371. [DOI] [PubMed] [Google Scholar]
375.Shandilya C, Mani S. Rho kinase isoforms in neurodegeneration: From cellular functions to therapeutic targets. Mol Biol Rep 2025;52:846. doi: 10.1007/s11033-025-10947-9. [DOI] [PubMed] [Google Scholar]
376.Shi W, Tan C, Liu C, Chen D. Mitochondrial fission mediated by Drp1-Fis1 pathway and neurodegenerative diseases. Rev Neurosci 2023;34:275-294. doi: 10.1515/revneuro-2022-0056. [DOI] [PubMed] [Google Scholar]
377.Wang J Zhuang H Jia L He X Zheng S Ji K, et al. Nuclear receptor subfamily 4 group A member 1 promotes myocardial ischemia/reperfusion injury through inducing mitochondrial fission factor-mediated mitochondrial fragmentation and inhibiting FUN14 domain containing 1-depedent mitophagy. Int J Biol Sci 2024;20:4458-4475. doi: 10.7150/ijbs.95853. [DOI] [PMC free article] [PubMed] [Google Scholar]
378.Zhang R Xue MY Liu BS Wang WJ Fan XH Zheng BY, et al. Aldehyde dehydrogenase 2 preserves mitochondrial morphology and attenuates hypoxia/reoxygenation-induced cardiomyocyte injury. World J Emerg Med 2020;11:246-254. doi: 10.5847/wjem.j.1920-8642.2020.04.007. [DOI] [PMC free article] [PubMed] [Google Scholar]
379.Ying J Deng X Du R Ding Q Tian H Lin Y, et al. Mitochondrial modulation treating postoperative cognitive dysfunction neuroprotection via DRP1 inhibition by Mdivi1. Sci Rep 2024;14:26155. doi: 10.1038/s41598-024-75548-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
380.Yao S Pang M Wang Y Wang X Lin Y Lv Y, et al. Mesenchymal stem cell attenuates spinal cord injury by inhibiting mitochondrial quality control-associated neuronal ferroptosis. Redox Biol 2023;67:102871. doi: 10.1016/j.redox.2023.102871. [DOI] [PMC free article] [PubMed] [Google Scholar]
381.Qin YR Ma CQ Jiang JH Wang DP Zhang QQ Liu MR, et al. Artesunate restores mitochondrial fusion-fission dynamics and alleviates neuronal injury in Alzheimer’s disease models. J Neurochem 2022;162:290-304. doi: 10.1111/jnc.15620. [DOI] [PubMed] [Google Scholar]
382.Qiu K Zou W Fang H Hao M Mehta K Tian Z, et al. Light-activated mitochondrial fission through optogenetic control of mitochondria-lysosome contacts. Nat Commun 2022;13:4303. doi: 10.1038/s41467-022-31970-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
383.Sun Y, He J, Bao L, Shi X, Wang J, Li Q. Harnessing exercise to combat chronic diseases: The role of Drp1-Mediated mitochondrial fission. Front Cell Dev Biol 2025;13:1481756. doi: 10.3389/fcell.2025.1481756. [DOI] [PMC free article] [PubMed] [Google Scholar]
384.Gu C, Yan J, Zhao L, Wu G, Wang YL. Regulation of mitochondrial dynamics by aerobic exercise in cardiovascular diseases. Front Cardiovasc Med 2021;8:788505. doi: 10.3389/fcvm.2021.788505. [DOI] [PMC free article] [PubMed] [Google Scholar]
385.Ma M, Chen W, Hua Y, Jia H, Song Y, Wang Y. Aerobic exercise ameliorates cardiac hypertrophy by regulating mitochondrial quality control and endoplasmic reticulum stress through M(2) AChR. J Cell Physiol 2021;236:6581-6596. doi: 10.1002/jcp.30342. [DOI] [PubMed] [Google Scholar]
386.Bauer BL, Rochon K, Liu JC, Ramachandran R, Mears JA. Disease-associated mutations in Drp1 have fundamentally different effects on the mitochondrial fission machinery. Hum Mol Genet 2023;32:1975-1987. doi: 10.1093/hmg/ddad029. [DOI] [PMC free article] [PubMed] [Google Scholar]
387.Jin JY, Wei XX, Zhi XL, Wang XH, Meng D. Drp1-dependent mitochondrial fission in cardiovascular disease. Acta Pharmacol Sin 2021;42:655-664. doi: 10.1038/s41401-020-00518-y. [DOI] [PMC free article] [PubMed] [Google Scholar]
388.Zerihun M, Sukumaran S, Qvit N. The Drp1-mediated mitochondrial fission protein interactome as an emerging core player in mitochondrial dynamics and cardiovascular disease therapy. Int J Mol Sci 2023;24:5785. doi: 10.3390/ijms24065785. [DOI] [PMC free article] [PubMed] [Google Scholar]
389.Lv ZM, Liu C, Wang P, Chen YH. Dysregulation of mitochondrial dynamics and mitophagy are involved in high-fat diet-induced steroidogenesis inhibition. J Lipid Res 2024;65:100639. doi: 10.1016/j.jlr.2024.100639. [DOI] [PMC free article] [PubMed] [Google Scholar]
390.Tu B Song K Zhou Y Sun H Liu ZY Lin LC, et al. METTL3 boosts mitochondrial fission and induces cardiac fibrosis by enhancing LncRNA GAS5 methylation. Pharmacol Res 2023;194:106840. doi: 10.1016/j.phrs.2023.106840. [DOI] [PubMed] [Google Scholar]
391.Si M Chen J Yu R Lin H Li F Jung S, et al. Protein kinase ROCK1 activates mitochondrial fission linking to oxidative stress and muscle atrophy. Kidney Int 2025;108:626-641. doi: 10.1016/j.kint.2025.05.019. [DOI] [PMC free article] [PubMed] [Google Scholar]
392.Wadan AS Shaaban AH El-Sadek MZ Mostafa SA Moshref AS El-Hussein A, et al. Mitochondrial-based therapies for neurodegenerative diseases: A review of the current literature. Naunyn Schmiedebergs Arch Pharmacol 2025;398:11357-11386. doi: 10.1007/s00210-025-04014-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
393.Curtis WM, Seeds WA, Mattson MP, Bradshaw PC. NADPH and mitochondrial quality control as targets for a circadian-based fasting and exercise therapy for the treatment of Parkinson’s disease. Cells 2022;11:2416. doi: 10.3390/cells11152416. [DOI] [PMC free article] [PubMed] [Google Scholar]
394.Zhang J, Qiao W, Luo Y. Mitochondrial quality control proteases and their modulation for cancer therapy. Med Res Rev 2023;43:399-436. doi: 10.1002/med.21929. [DOI] [PubMed] [Google Scholar]
395.Wu L, Wang L, Du Y, Zhang Y, Ren J. Mitochondrial quality control mechanisms as therapeutic targets in doxorubicin-induced cardiotoxicity. Trends Pharmacol Sci 2023;44:34-49. doi: 10.1016/j.tips.2022.10.003. [DOI] [PubMed] [Google Scholar]
396.Li W Zhang Y Wei Y Ling G Zhang Y Li Y, et al. New insights into mitochondrial quality control in anthracycline-induced cardiotoxicity: Molecular mechanisms, therapeutic targets, and natural products. Int J Biol Sci 2025;21:507-523. doi: 10.7150/ijbs.103810. [DOI] [PMC free article] [PubMed] [Google Scholar]
397.Bai Y, Wu J, Yang Z, Wang X, Zhang D, Ma J. Mitochondrial quality control in cardiac ischemia/reperfusion injury: New insights into mechanisms and implications. Cell Biol Toxicol 2023;39:33-51. doi: 10.1007/s10565-022-09716-2. [DOI] [PubMed] [Google Scholar]
398.Ye W Han K Xie M Li S Chen G Wang Y, et al. Mitochondrial energy metabolism in diabetic cardiomyopathy: Physiological adaption, pathogenesis, and therapeutic targets. Chin Med J 2024;137:936-948. doi: 10.1097/CM9.0000000000003075. [DOI] [PMC free article] [PubMed] [Google Scholar]
399.Zhang T Wang L Duan X Niu Y Li M Yun L, et al. Sirtuins mediate mitochondrial quality control mechanisms: A novel therapeutic target for osteoporosis. Front Endocrinol (Lausanne) 2023;14:1281213. doi: 10.3389/fendo.2023.1281213. [DOI] [PMC free article] [PubMed] [Google Scholar]
400.Liu J Wang J Xiong A Zhang L Zhang Y Liu Y, et al. Mitochondrial quality control in lung diseases: Current research and future directions. Front Physiol 2023;14:1236651. doi: 10.3389/fphys.2023.1236651. [DOI] [PMC free article] [PubMed] [Google Scholar]
401.Xu M, Feng P, Yan J, Li L. Mitochondrial quality control: A pathophysiological mechanism and potential therapeutic target for chronic obstructive pulmonary disease. Front Pharmacol 2024;15:1474310. doi: 10.3389/fphar.2024.1474310. [DOI] [PMC free article] [PubMed] [Google Scholar]
402.Yao C, Li Z, Sun K, Zhang Y, Shou S, Jin H. Mitochondrial dysfunction in acute kidney injury. Ren Fail 2024;46:2393262. doi: 10.1080/0886022X.2024.2393262. [DOI] [PMC free article] [PubMed] [Google Scholar]
403.Chen L Yang J Cai Z Huang Y Zhang Q Zhou C, et al. Cerium dioxide nanoparticles-based inspector enhances mitochondrial quality control to maintain chondrocyte homeostasis in osteoarthritis therapy. Adv Healthc Mater 2025;14:e2405069. doi: 10.1002/adhm.202405069. [DOI] [PubMed] [Google Scholar]
404.Jia L, Yang Y, Sun F, Tao H, Lu C, Yang JJ. Mitochondrial quality control in liver fibrosis: Epigenetic hallmarks and therapeutic strategies. Cell Signal 2024;115:111035. doi: 10.1016/j.cellsig.2024.111035. [DOI] [PubMed] [Google Scholar]
405.Sharafi F, Rismani E, Rhmanian M, Khosravi A, Zarrabi A, Vosough M. Mitochondrial dysfunction in hepatocellular carcinoma: From metabolism to targeted therapies. Mol Cell Biochem 2025;480:6015-6038. doi: 10.1007/s11010-025-05377-x. [DOI] [PubMed] [Google Scholar]
406.Wang L, Zhou X, Lu T. Role of mitochondria in physiological activities, diseases, and therapy. Mol Biomed 2025;6:42. doi: 10.1186/s43556-025-00284-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
407.Hou D Liu R Hao S Dou Y Chen G Liu L, et al. Notoginsenoside R1 improves intestinal microvascular functioning in sepsis by targeting Drp1-mediated mitochondrial quality imbalance. Pharm Biol 2024;62:250-260. doi: 10.1080/13880209.2024.2318349. [DOI] [PMC free article] [PubMed] [Google Scholar]
408.Tian L Jia Z Yan Y Jia Q Shi W Cui S, et al. Low-dose of caffeine alleviates high altitude pulmonary edema via regulating mitochondrial quality control process in AT1 cells. Front Pharmacol 2023;14:1155414. doi: 10.3389/fphar.2023.1155414. [DOI] [PMC free article] [PubMed] [Google Scholar]
409.Son YS Kwon YH Lee MS Kwon O Jeong YJ Mun SJ, et al. Helicobacter pylori VacA-induced mitochondrial damage in the gastric pit cells of the antrum and therapeutic rescue. Biomaterials 2025;314:122842. doi: 10.1016/j.biomaterials.2024.122842. [DOI] [PubMed] [Google Scholar]
410.Jang HJ, Kim YY, Lee KM, Shin JE, Yun J. The PINK1 activator niclosamide mitigates mitochondrial dysfunction and thermal hypersensitivity in a paclitaxel-induced drosophila model of peripheral neuropathy. Biomedicines 2022;10:863. doi: 10.3390/biomedicines10040863. [DOI] [PMC free article] [PubMed] [Google Scholar]
411.Feng Y Goncalves MM Jitkova Y Keszei AFA Yan Y Sarathy C, et al. Serine phosphorylation facilitates protein degradation by the human mitochondrial ClpXP protease. Proc Natl Acad Sci U S A 2025;122:e2422447122. doi: 10.1073/pnas.2422447122. [DOI] [PMC free article] [PubMed] [Google Scholar]
412.Cen X, Xu X, Xia H. Targeting MCL1 to induce mitophagy is a potential therapeutic strategy for Alzheimer disease. Autophagy 2021;17:818-819. doi: 10.1080/15548627.2020.1860542. [DOI] [PMC free article] [PubMed] [Google Scholar]
413.Dong Y Zhuang XX Wang YT Tan J Feng D Li M, et al. Chemical mitophagy modulators: Drug development strategies and novel regulatory mechanisms. Pharmacol Res 2023;194:106835. doi: 10.1016/j.phrs.2023.106835. [DOI] [PubMed] [Google Scholar]
414.Rodriguez YA, Kaur S, Nolte E, Zheng Z, Blagg BSJ, Dobrowsky RT. Novologue therapy requires heat shock protein 70 and thioredoxin-interacting protein to improve mitochondrial bioenergetics and decrease mitophagy in diabetic sensory neurons. ACS Chem Neurosci 2021;12:3049-3059. doi: 10.1021/acschemneuro.1c00340. [DOI] [PMC free article] [PubMed] [Google Scholar]
415.Palabiyik AA, Palabiyik E. Pharmacological approaches to enhance mitochondrial biogenesis: Focus on PGC-1Alpha, AMPK, and SIRT1 in cellular health. Mol Biol Rep 2025;52:270. doi: 10.1007/s11033-025-10368-8. [DOI] [PubMed] [Google Scholar]
416.Zhong YL Xu CQ Li J Liang ZQ Wang MM Ma C, et al. Mitochondrial dynamics and metabolism in macrophages for cardiovascular disease: A review. Phytomedicine 2025;140:156620. doi: 10.1016/j.phymed.2025.156620. [DOI] [PubMed] [Google Scholar]
417.Kong L Liu Y Wang JH Lv MJ Wang YZ Sun WP, et al. Linggui Zhugan decoction ameliorating mitochondrial damage of doxorubicin-induced cardiotoxicity by modulating the AMPK-FOXO3a pathway targeting BTG2. Phytomedicine 2025;139:156529. doi: 10.1016/j.phymed.2025.156529. [DOI] [PubMed] [Google Scholar]
418.Lee JY, Lim W, Song G. Tumor-suppressive function of methiothepin in human placental choriocarcinoma cells. Reproduction 2020;160:919-929. doi: 10.1530/REP-20-0377. [DOI] [PubMed] [Google Scholar]
419.Cerqueira FM Kozer N Petcherski A Baranovski BM Wolf D Assali EA, et al. MitoTimer-based high-content screen identifies two chemically-related benzothiophene derivatives that enhance basal mitophagy. Biochem J 2020;477:461-475. doi: 10.1042/BCJ20190616. [DOI] [PubMed] [Google Scholar]
420.Kodam P, Kumar V, Pattanayak P, Vitta P, Chatterjee T, Maity S. Novel small molecule derivatives improve survivability in the cellular model of Huntington’s disease via improving mitochondrial fusion. RSC Med Chem 2025;17:705-722. doi: 10.1039/d5md00345h. [DOI] [PMC free article] [PubMed] [Google Scholar]
421.Gubic S Hendrickx LA Toplak Z Sterle M Peigneur S Tomasic T, et al. Discovery of K(V) 1.3 ion channel inhibitors: Medicinal chemistry approaches and challenges. Med Res Rev 2021;41:2423-2473. doi: 10.1002/med.21800. [DOI] [PMC free article] [PubMed] [Google Scholar]
422.Kazi NH, Klink N, Gallant K, Kipka GM, Gersch M. Chimeric deubiquitinase engineering reveals structural basis for specific inhibition of the mitophagy regulator USP30. Nat Struct Mol Biol 2025;32:1776-1786. doi: 10.1038/s41594-025-01534-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
423.Ren Y Wu LL Song W Gao Y Shao L Lu Z, et al. Mitochondrial electron flow dynamics imaging for assessing mitochondrial quality and drug screening. Adv Sci (Weinh) 2025;12:e2410561. doi: 10.1002/advs.202410561. [DOI] [PMC free article] [PubMed] [Google Scholar]
424.Debnath P. Organic fluorophores conjugated with pyridinium acceptor: A Review on design, synthesis, and application in mitochondrial imaging. Curr Pharm Des 2026;32:971-1001. doi: 10.2174/0113816128395084250708080830. [DOI] [PubMed] [Google Scholar]
425.Qiao J, Liu Y, Ma Z, Zhao X, Feng Y. Quantifying mitochondrial viscosity changes by an AIE probe during drug therapy. Chem Commun (Camb) 2025;61:11037-11040. doi: 10.1039/d5cc01021g. [DOI] [PubMed] [Google Scholar]
426.Feng X, Cai W, Li Q, Zhao L, Meng Y, Xu H. Activation of lysosomal Ca2+ channels mitigates mitochondrial damage and oxidative stress. J Cell Biol 2025;224:e202403104. doi: 10.1083/jcb.202403104. [DOI] [PMC free article] [PubMed] [Google Scholar]
427.Liu M, Ji W, Zhao X, Liu X, Hu JF, Cui J. Therapeutic potential of engineering the mitochondrial genome. Biochim Biophys Acta Mol Basis Dis 2023;1869:166804. doi: 10.1016/j.bbadis.2023.166804. [DOI] [PubMed] [Google Scholar]
428.Falabella M, Minczuk M, Hanna MG, Viscomi C, Pitceathly RDS. Gene therapy for primary mitochondrial diseases: Experimental advances and clinical challenges. Nat Rev Neurol 2022;18:689-698. doi: 10.1038/s41582-022-00715-9. [DOI] [PubMed] [Google Scholar]
429.Tang JX, Pyle A, Taylor RW, Olahova M. Interrogating mitochondrial biology and disease using CRISPR/Cas9 gene editing. Genes (Basel) 2021;12:1604. doi: 10.3390/genes12101604. [DOI] [PMC free article] [PubMed] [Google Scholar]
430.Wang Y, Wang Y, Chen Y, Yan Q, Lin A. Research progress in mitochondrial gene editing technology (in Chinese). Journal of Zhejiang University (Medical Sciences) 2023;52:460-472. doi: 10.3724/zdxbyxb-2023-0129. [DOI] [PMC free article] [PubMed] [Google Scholar]
431.Gao Y, Guo L, Wang F, Wang Y, Li P, Zhang D. Development of mitochondrial gene-editing strategies and their potential applications in mitochondrial hereditary diseases: A review. Cytotherapy 2024;26:11-24. doi: 10.1016/j.jcyt.2023.10.004. [DOI] [PubMed] [Google Scholar]
432.Slone J, Huang T. The special considerations of gene therapy for mitochondrial diseases. NPJ Genom Med 2020;5:7. doi: 10.1038/s41525-020-0116-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
433.Guo Y Zhang K Gao X Zhou Z Liu Z Yang K, et al. Sustained oligomycin sensitivity conferring protein expression in cardiomyocytes protects against cardiac hypertrophy induced by pressure overload via improving mitochondrial function. Hum Gene Ther 2020;31:1178-1189. doi: 10.1089/hum.2020.004. [DOI] [PMC free article] [PubMed] [Google Scholar]
434.Keshavan N Greenwood M Prunty H Diaz JA Privolizzi R Counsell J, et al. Gene therapy prevents hepatic mitochondrial dysfunction in murine deoxyguanosine kinase deficiency. Mol Ther Methods Clin Dev 2025;33:101397. doi: 10.1016/j.omtm.2024.101397. [DOI] [PMC free article] [PubMed] [Google Scholar]
435.Pares M Fornaguera C Vila-Julia F Oh S Fan SHY Tam YK, et al. Preclinical assessment of a gene-editing approach in a mouse model of mitochondrial neurogastrointestinal encephalomyopathy. Hum Gene Ther 2021;32:1210-1223. doi: 10.1089/hum.2021.152. [DOI] [PubMed] [Google Scholar]
436.Cho YW, Yoon J, Song SG, Noh YW. Mitochondrial DNA as a target for analyzing the biodistribution of cell therapy products. Sci Rep 2024;14:7934. doi: 10.1038/s41598-024-56591-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
437.Zhang X Huang L Li C Yang J Duan F Su Q, et al. Gene therapy prevents onset of mitochondrial cardiomyopathy in neonatal mice with Ndufs6 deficiency. Cell Death Discov 2025;11:249. doi: 10.1038/s41420-025-02524-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
438.Li H Sun B Huang Y Zhang J Xu X Shen Y, et al. Gene therapy of yeast NDI1 on mitochondrial complex I dysfunction in rotenone-induced Parkinson’s disease models in vitro and vivo. Mol Med 2022;28:29. doi: 10.1186/s10020-022-00456-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
439.Li H Chen Z Shen Y Xiong T Chen A Chen L, et al. Gene therapy in Abeta-induced cell and mouse models of Alzheimer’s disease through compensating defective mitochondrial complex I function. J Transl Med 2024;22:760. doi: 10.1186/s12967-024-05571-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
440.Chemello F Pozzobon M Tsansizi LI Varanita T Quintana-Cabrera R Bonesso D, et al. Dysfunctional mitochondria accumulate in a skeletal muscle knockout model of Smn1, the causal gene of spinal muscular atrophy. Cell Death Dis 2023;14:162. doi: 10.1038/s41419-023-05573-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
441.She M Huang M Zhang J Yan Y Zhou L Zhang M, et al. Astragulus embranaceus (Fisch.) Bge-Dioscorea opposita Thunb herb pair ameliorates sarcopenia in senile type 2 diabetes mellitus through Rab5a/mTOR-mediated mitochondrial dysfunction. J Ethnopharmacol 2023;317:116737. doi: 10.1016/j.jep.2023.116737. [DOI] [PubMed] [Google Scholar]
442.Base editing ablates all protein-coding genes of the mitochondrial genome in mouse cells. Nat Biomed Eng 2023;7:614-615. doi: 10.1038/s41551-022-00986-z. [DOI] [PubMed] [Google Scholar]
443.Hanaford AR, Cho YJ, Nakai H. AAV-vector based gene therapy for mitochondrial disease: Progress and future perspectives. Orphanet J Rare Dis 2022;17:217. doi: 10.1186/s13023-022-02324-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
444.Na JH, Lee YM. Therapeutic approach to epilepsy in patients with mitochondrial diseases. Yonsei Med J 2025;66:131-140. doi: 10.3349/ymj.2024.0325. [DOI] [PMC free article] [PubMed] [Google Scholar]
445.Nishida R Nukaga S Kawahara I Miyagawa Y Goto K Nakashima C, et al. Differential effects of three medium-chain fatty acids on mitochondrial quality control and skeletal muscle maturation. Antioxidants (Basel) 2024;13:821. doi: 10.3390/antiox13070821. [DOI] [PMC free article] [PubMed] [Google Scholar]
446.Azzolino D Bertoni C De Cosmi V Spolidoro GCI Agostoni C Lucchi T, et al. Omega-3 polyunsatured fatty acids and physical performance across the lifespan: A narrative review. Front Nutr 2024;11:1414132. doi: 10.3389/fnut.2024.1414132. [DOI] [PMC free article] [PubMed] [Google Scholar]
447.Wang Y Sun J Xue L Sun Y Zhang K Fan M, et al. Chlorogenic acid improves high-fat diet-induced skeletal muscle metabolic disorders by regulating mitochondrial function and lactate metabolism. J Agric Food Chem 2025;73:10347-10357. doi: 10.1021/acs.jafc.5c03967. [DOI] [PubMed] [Google Scholar]
448.Cheng K Yao J Song Z Huang J Zhao H Yang R, et al. Effects of resveratrol on redox status, jejunal injury, and mitochondrial function in intrauterine growth-retarded weaned piglets. Animals (Basel) 2025;15:290. doi: 10.3390/ani15030290. [DOI] [PMC free article] [PubMed] [Google Scholar]
449.Nederveen JP Mastrolonardo AJ Xhuti D Di Carlo A Manta K Fuda MR, et al. Novel multi-ingredient supplement facilitates weight loss and improves body composition in overweight and obese individuals: A randomized, double-blind, placebo-controlled clinical trial. Nutrients 2023;15:3693. doi: 10.3390/nu15173693. [DOI] [PMC free article] [PubMed] [Google Scholar]
450.Mercurio G Giacco A Scopigno N Vigliotti M Goglia F Cioffi F, et al. Mitochondria at the crossroads: Linking the mediterranean diet to metabolic health and non-pharmacological approaches to NAFLD. Nutrients 2025;17:1214. doi: 10.3390/nu17071214. [DOI] [PMC free article] [PubMed] [Google Scholar]
451.You Y Ni H Ma Q Jiang L Cai J He W, et al. Ketogenic diet ameliorates MASLD via balancing mitochondrial dynamics and improving mitochondrial dysfunction. Nutr Diabetes 2025;15:37. doi: 10.1038/s41387-025-00391-w. [DOI] [PMC free article] [PubMed] [Google Scholar]
452.Na JH, Kim HD, Lee YM. Effective and safe diet therapies for Lennox-Gastaut syndrome with mitochondrial dysfunction. Ther Adv Neurol Disord 2020;13:1756286419897813. doi: 10.1177/1756286419897813. [DOI] [PMC free article] [PubMed] [Google Scholar]
453.Dzotsi M Strohm A Varshney S Zuniga-Hertz JP Chitteti R Manoogian E, et al. Time-restricted eating improves quality of life, heart rate, and mitochondrial function in patients with postural orthostatic tachycardia syndrome. medRxiv 2025:2025.05.29.25328448. doi: 10.1101/2025.05.29.25328448. [DOI] [PMC free article] [PubMed] [Google Scholar]
454.Tomtheelnganbee E, Sah P, Sharma R. Mitochondrial function and nutrient sensing pathways in ageing: Enhancing longevity through dietary interventions. Biogerontology 2022;23:657-680. doi: 10.1007/s10522-022-09978-7. [DOI] [PubMed] [Google Scholar]
455.Widjaja S, Antarianto RD, Hardiany NS. Effects of dietary restriction on PGC-1alpha regulation in the development of age-associated diseases. Curr Aging Sci 2024;17:189-195. doi: 10.2174/0118746098301226240402051508. [DOI] [PubMed] [Google Scholar]
456.Fuentes-Barria H Aguilera-Eguia R Angarita-Davila L Rojas-Gomez D Alarcon-Rivera M Lopez-Soto O, et al. Vitamin D and sarcopenia: Implications for muscle health. Biomedicines 2025;13:1863. doi: 10.3390/biomedicines13081863. [DOI] [PMC free article] [PubMed] [Google Scholar]
457.Killilea DW, Killilea AN. Mineral requirements for mitochondrial function: A connection to redox balance and cellular differentiation. Free Radic Biol Med 2022;182:182-191. doi: 10.1016/j.freeradbiomed.2022.02.022. [DOI] [PubMed] [Google Scholar]
458.Choi SE Hwang Y Lee SJ Jung H Shin TH Son Y, et al. Mitochondrial protease ClpP supplementation ameliorates diet-induced NASH in mice. J Hepatol 2022;77:735-747. doi: 10.1016/j.jhep.2022.03.034. [DOI] [PubMed] [Google Scholar]
459.Liu S Faitg J Tissot C Konstantopoulos D Laws R Bourdier G, et al. Urolithin A provides cardioprotection and mitochondrial quality enhancement preclinically and improves human cardiovascular health biomarkers. iScience 2025;28: 111814. doi: 10.1016/j.isci.2025.111814. [DOI] [PMC free article] [PubMed] [Google Scholar]
460.Broome SC, Whitfield J, Karagounis LG, Hawley JA. Mitochondria as nutritional targets to maintain muscle health and physical function during ageing. Sports Med 2024;54:2291-2309. doi: 10.1007/s40279-024-02072-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
461.Handayani D, Handayani A, Rudijanto A, Nuraissa P, Rahmawati W, Huang XF. Effects of brown rice, meal replacements, and anti-obesity drugs on mitochondria in obese rats. Diabetes Metab Syndr Obes 2025;18:3151-3165. doi: 10.2147/DMSO.S535983. [DOI] [PMC free article] [PubMed] [Google Scholar]
462.Nagpal D, Nema S, Nagpal S, Pandey MM, Kaushik D, Kathuria H. Management and prevention of neurodegenerative disorders: Can antioxidant-rich dietary interventions help? Antioxidants (Basel) 2025;14:1078. doi: 10.3390/antiox14091078. [DOI] [PMC free article] [PubMed] [Google Scholar]
463.Jun L, Tao YX, Geetha T, Babu JR. Mitochondrial adaptation in skeletal muscle: Impact of obesity, caloric restriction, and dietary compounds. Curr Nutr Rep 2024;13:500-515. doi: 10.1007/s13668-024-00555-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
464.Prem PN, Kurian GA. High-fat diet increased oxidative stress and mitochondrial dysfunction induced by renal ischemia-reperfusion injury in rat. Front Physiol 2021;12:715693. doi: 10.3389/fphys.2021.715693. [DOI] [PMC free article] [PubMed] [Google Scholar]
465.Han X Zhang B Gong Q Liu T Wang C Sun Y, et al. The tolerable upper intake level of manganese alleviates Parkinson-like motor performance and neuronal loss by activating mitophagy. Free Radic Biol Med 2024;225:665-676. doi: 10.1016/j.freeradbiomed.2024.10.281. [DOI] [PubMed] [Google Scholar]
466.Lima MR, Moreira BJ, Bertuzzi R, Lima-Silva AE. Could nanotechnology improve exercise performance? Evidence from animal studies. Braz J Med Biol Res 2024;57:e13360. doi: 10.1590/1414-431X2024e13360. [DOI] [PMC free article] [PubMed] [Google Scholar]
467.Golpour-Hamedani S, Bagherniy M, Khorvash F, Feizi A, Sharma M, Askari G. Investigating the effects of co-supplementation with alpha-linolenic acid and L-carnitine on inflammatory status, oxidative stress, clinical symptoms, mental health and quality of life in women with migraine: A protocol for a randomized, triple-blind, placebo-controlled trial. Trials 2024;25:666. doi: 10.1186/s13063-024-08500-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
468.Jiao Q, Xiang L, Chen Y. Mitochondrial transplantation: A promising therapy for mitochondrial disorders. Int J Pharm 2024;658:124194. doi: 10.1016/j.ijpharm.2024.124194. [DOI] [PubMed] [Google Scholar]
469.Chernyak BV. Mitochondrial transplantation: A critical analysis. Biochemistry (Mosc) 2020;85:636-641. doi: 10.1134/S0006297920050132. [DOI] [PubMed] [Google Scholar]
470.Cao M Zou J Shi M Zhao D Liu C Liu Y, et al. A promising therapeutic: Exosome-mediated mitochondrial transplantation. Int Immunopharmacol 2024;142:113104. doi: 10.1016/j.intimp.2024.113104. [DOI] [PubMed] [Google Scholar]
471.Nakano T, Irie K, Matsuo K, Mishima K, Nakamura Y. Molecular and cellular mechanisms of mitochondria transfer in models of central nervous system disease. J Cereb Blood Flow Metab 2026;46:269-288. doi: 10.1177/0271678X241300223. [DOI] [PMC free article] [PubMed] [Google Scholar]
472.Lim GB. Intracoronary mitochondrial transplantation. Nat Rev Cardiol 2020;17:131. doi: 10.1038/s41569-020-0340-9. [DOI] [PubMed] [Google Scholar]
473.Doulamis IP, McCully JD. Mitochondrial transplantation for ischemia reperfusion injury. Methods Mol Biol 2021;2277:15-37. doi: 10.1007/978-1-0716-1270-5_2. [DOI] [PubMed] [Google Scholar]
474.Wang LJ Guo PF Zhang S Wang S Chen YZ Yan HW, et al. Mitochondrial transfer/transplantation in lung injury: Mechanism, therapeutic potential, and clinical application. Front Immunol 2025;16:1668281. doi: 10.3389/fimmu.2025.1668281. [DOI] [PMC free article] [PubMed] [Google Scholar]
475.Iwata K, Noguchi M, Shintani N. Mitochondrial transplantation in animal models of psychiatric disorders: A novel approach to psychiatric treatment. Biomolecules 2025;15:184. doi: 10.3390/biom15020184. [DOI] [PMC free article] [PubMed] [Google Scholar]
476.McCully JD, Del Nido PJ, Emani SM. Mitochondrial transplantation for organ rescue. Mitochondrion 2022;64:27-33. doi: 10.1016/j.mito.2022.02.007. [DOI] [PubMed] [Google Scholar]
477.Baharvand F Habibi Roudkenar M Pourmohammadi-Bejarpasi Z Najafi-Ghalehlou N Feizkhah A Bashiri Aliabadi S, et al. Safety and efficacy of platelet-derived mitochondrial transplantation in ischaemic heart disease. Int J Cardiol 2024;410:132227. doi: 10.1016/j.ijcard.2024.132227. [DOI] [PubMed] [Google Scholar]
478.Joore IP Shehata S Muffels I Castro-Alpizar J Jimenez-Curiel E Nagyova E, et al. Correction of pathogenic mitochondrial DNA in patient-derived disease models using mitochondrial base editors. PLoS Biol 2025;23:e3003207. doi: 10.1371/journal.pbio.3003207. [DOI] [PMC free article] [PubMed] [Google Scholar]
479.Lim K. Mitochondrial genome editing: Strategies, challenges, and applications. BMB Rep 2024;57:19-29. doi: 10.5483/BMBRep.2023-0224. [DOI] [PMC free article] [PubMed] [Google Scholar]
480.Kubat GB, Ulger O, Akin S. Requirements for successful mitochondrial transplantation. J Biochem Mol Toxicol 2021;35:e22898. doi: 10.1002/jbt.22898. [DOI] [PubMed] [Google Scholar]
481.Zhang TG, Miao CY. Mitochondrial transplantation as a promising therapy for mitochondrial diseases. Acta Pharm Sin B 2023;13:1028-1035. doi: 10.1016/j.apsb.2022.10.008. [DOI] [PMC free article] [PubMed] [Google Scholar]
482.Toosky M, Kheradvar A. Assessment of mitochondrial viability under calcium stress: Insights for mitochondrial transplantation. Mitochondrion 2025;86:102098. doi: 10.1016/j.mito.2025.102098. [DOI] [PMC free article] [PubMed] [Google Scholar]
483.Li M Wu L Si H Wu Y Liu Y Zeng Y, et al. Engineered mitochondria in diseases: Mechanisms, strategies, and applications. Signal Transduct Target Ther 2025;10:71. doi: 10.1038/s41392-024-02081-y. [DOI] [PMC free article] [PubMed] [Google Scholar]
484.Bodenstein DF Siebiger G Zhao Y Clasky AJ Mukkala AN Beroncal EL, et al. Bridging the gap between in vitro and in vivo models: A way forward to clinical translation of mitochondrial transplantation in acute disease states. Stem Cell Res Ther 2024;15:157. doi: 10.1186/s13287-024-03771-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
485.Wu J, Xu J, Zhang M, Zhong J, Gao W, Wu M. Chondrocyte mitochondrial quality control: A novel insight into osteoarthritis and cartilage regeneration. Adv Wound Care (New Rochelle) 2026;15:50-70. doi: 10.1089/wound.2024.0270. [DOI] [PubMed] [Google Scholar]
486.Wu S, Bakky MAH, Zhang M, Tran NT, Li S. Harnessing mitochondrial quality control in oxidative stress and environmental resilience in aquaculture. Vet Res Commun 2026;50:121. doi: 10.1007/s11259-025-11051-w. [DOI] [PubMed] [Google Scholar]
487.Liu H Huang S Chen S Liang S Huang M Li S, et al. Pharmacological potential of Chinese botanical drugs in managing chronic kidney disease by targeting mitochondrial quality control. Front Pharmacol 2025;16:1725842. doi: 10.3389/fphar.2025.1725842. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R1] 1.Schirrmacher V. Mitochondria at work: New Insights into regulation and dysregulation of cellular energy supply and metabolism. Biomedicines 2020;8:526. doi: 10.3390/biomedicines8110526. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R2] 2.Liu D Fan YB Tao XH Pan WL Wu YX Wang XH, et al. Mitochondrial quality control in sarcopenia: Updated overview of mechanisms and interventions. Aging Dis 2021;12:2016-2030. doi: 10.14336/AD.2021.0427. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R3] 3.Weber-Stiehl S, Jarke L, Castrillon-Betancur JC, Gilbert F, Sommer F. Mitochondrial function and microbial metabolites as central regulators of intestinal immune responses and cancer. Front Microbiol 2022;13:919424. doi: 10.3389/fmicb.2022.919424. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R4] 4.Li XD, Zuo SY, Xu LP, Song YP, Li W. Advances in macrophage metabolic reprogramming in hematological malignancies. Chin Med J BioMed 2025. doi: 10.65457/CMJBM-2025-0001. [Google Scholar]

[R5] 5.Jadiya P, Tomar D. Mitochondrial protein quality control mechanisms. Genes (Basel) 2020;11:563. doi: 10.3390/genes11050563. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R6] 6.Tomar MS, Kumar A, Shrivastava A. Mitochondrial metabolism as a dynamic regulatory hub to malignant transformation and anti-cancer drug resistance. Biochem Biophys Res Commun 2024;694:149382. doi: 10.1016/j.bbrc.2023.149382. [DOI] [PubMed] [Google Scholar]

[R7] 7.Santos EW, Khatoon S, Di Mise A, Zheng YM, Wang YX. Mitochondrial dynamics in pulmonary hypertension. Biomedicines 2023;12:53. doi: 10.3390/biomedicines12010053. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R8] 8.Li S Zhang J Liu C Wang Q Yan J Hui L, et al. The role of mitophagy in regulating cell death. Oxid Med Cell Longev 2021;2021:6617256. doi: 10.1155/2021/6617256. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R9] 9.Changaei M Azimzadeh Tabrizi Z Karimi M Kashfi SA Koochaki Chahardeh T Hashemi SM, et al. From powerhouse to modulator: Regulating immune system responses through intracellular mitochondrial transfer. Cell Commun Signal 2025;23:232. doi: 10.1186/s12964-025-02237-5. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R10] 10.Chen Y Liu X Liu Y Li Y Li D Mei Z, et al. Mitochondrial quality control in diabetes mellitus and complications: Molecular mechanisms and therapeutic strategies. Cell Death Dis 2025;16:652. doi: 10.1038/s41419-025-07936-y. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R11] 11.Feng YF, Jin XR, Song JK, Hu J. Immunological tolerance and neurohomeostasis imbalance: Regulatory axis of neuropsychiatric diseases and new perspectives for intervention. Chin Med J BioMed. doi: 10.65457/CMJBM-2026-0001. [Google Scholar]

[R12] 12.Wang Q, Yuan Y, Liu J, Li C, Jiang X. The role of mitochondria in aging, cell death, and tumor immunity. Front Immunol 2024;15:1520072. doi: 10.3389/fimmu.2024.1520072. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R13] 13.Eldeeb MA, Thomas RA, Ragheb MA, Fallahi A, Fon EA. Mitochondrial quality control in health and in Parkinson’s disease. Physiol Rev 2022;102:1721-1755. doi: 10.1152/physrev.00041.2021. [DOI] [PubMed] [Google Scholar]

[R14] 14.Pal C. Targeting mitochondria with small molecules: A promising strategy for combating Parkinson’s disease. Mitochondrion 2024;79:101971. doi: 10.1016/j.mito.2024.101971. [DOI] [PubMed] [Google Scholar]

[R15] 15.Cho SI Lee S Mok YG Lim K Lee J Lee JM, et al. Targeted A-to-G base editing in human mitochondrial DNA with programmable deaminases. Cell 2022;185:1764-1776.e12. doi: 10.1016/j.cell.2022.03.039. [DOI] [PubMed] [Google Scholar]

[R16] 16.Mweene BC, Hatwiko H, Povia JP, Masenga SK. The role of mitochondrial dysfunction and dynamics in hypertensive heart disease: Mechanisms and recent advances. Biology (Basel) 2025;14:1212. doi: 10.3390/biology14091212. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R17] 17.Liu AM, Xu WL, Xiao H, Dong ED. Cardiac beta-adrenergic receptor regulation of mitochondrial function in heart failure (in Chinese). Acta Physiologica Sinica 2024;76:865-880. [PubMed] [Google Scholar]

[R18] 18.Li Y Wang P Yang H He J Yang Y Tao Y, et al. In vivo identification of bioactive components of Poria cocos for adjusting mitochondria against metabolic dysfunction-associated fatty liver disease. Heliyon 2024;10:e35645. doi: 10.1016/j.heliyon.2024.e35645. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R19] 19.Cai Y Gan F Chen Y He Q Chen W Peng Z, et al. Mitochondria as a therapeutic target in metabolic disorders. Mini Rev Med Chem 2025. doi: 10.2174/0113895575403490250917111723. [DOI] [PubMed] [Google Scholar]

[R20] 20.Wang SF, Tseng LM, Lee HC. Role of mitochondrial alterations in human cancer progression and cancer immunity. J Biomed Sci 2023;30:61. doi: 10.1186/s12929-023-00956-w. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R21] 21.Renaud CCN Trillet K Jardine J Merlet L Renoult O Laurent-Blond M, et al. The centrosomal protein 131 participates in the regulation of mitochondrial apoptosis. Commun Biol 2023;6:1271. doi: 10.1038/s42003-023-05676-3. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R22] 22.Kuznetsov AV, Javadov S, Margreiter R, Hagenbuchner J, Ausserlechner MJ. Analysis of mitochondrial function, structure, and intracellular organization in situ in cardiomyocytes and skeletal muscles. Int J Mol Sci 2022;23:2252. doi: 10.3390/ijms23042252. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R23] 23.Fan H, Tan Y. Lipid droplet-mitochondria contacts in health and disease. Int J Mol Sci 2024;25:5878. doi: 10.3390/ijms25136878. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R24] 24.Stork BA, Dean A, York B. Methodology for measuring oxidative capacity of isolated peroxisomes in the Seahorse assay. J Biol Methods 2022;9: e160. doi: 10.14440/jbm.2022.374. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R25] 25.Joshi AS. Peroxisomal membrane contact sites in yeasts. Front Cell Dev Biol 2021;9:735031. doi: 10.3389/fcell.2021.735031. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R26] 26.Taghizadeh-Hesary F, Akbari H, Bahadori M, Behnam B. Targeted anti-mitochondrial therapy: The future of oncology. Genes (Basel) 2022;13:1728. doi: 10.3390/genes13101728. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R27] 27.Zhang X Zhang X Ren J Li J Wei X Yu Y, et al. Precise modelling of mitochondrial diseases using optimized mitoBEs. Nature 2025;639:735-745. doi: 10.1038/s41586-024-08469-8. [DOI] [PubMed] [Google Scholar]

[R28] 28.Mi L Li YX Lv X Wan ZL Liu X Zhang K, et al. Computational design of a high-precision mitochondrial DNA cytosine base editor. Nat Struct Mol Biol 2025;32:2575-2586. doi: 10.1038/s41594-025-01714-2. [DOI] [PubMed] [Google Scholar]

[R29] 29.Jia Y Han L Ramage CL Wang Z Weng CC Yang L, et al. Co-targeting BCL-XL and BCL-2 by PROTAC 753B eliminates leukemia cells and enhances efficacy of chemotherapy by targeting senescent cells. Haematologica 2023;108:2626-2638. doi: 10.3324/haematol.2022.281915. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R30] 30.DiGiovanni LF Khroud PK Carmichael RE Schrader TA Gill SK Germain K, et al. ROS transfer at peroxisome-mitochondria contact regulates mitochondrial redox. Science 2025;389:157-162. doi: 10.1126/science.adn2804. [DOI] [PubMed] [Google Scholar]

[R31] 31.Koch C, Lenhard S, Raschle M, Prescianotto-Baschong C, Spang A, Herrmann JM. The ER-SURF pathway uses ER-mitochondria contact sites for protein targeting to mitochondria. EMBO Rep 2024;2:2071-2096. doi: 10.1038/s44319-024-00113-w. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R32] 32.Zhang H Yu X Ye J Li H Hu J Tan Y, et al. Systematic investigation of mitochondrial transfer between cancer cells and T cells at single-cell resolution. Cancer Cell 2023;41:1788-1802.e10. doi: 10.1016/j.ccell.2023.09.003. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R33] 33.Wang Y Yu HY Yi ZJ Qi LY Yang JS Xie HX, et al. Super mitochondria-enriched extracellular vesicles enable enhanced mitochondria transfer. Nat Commun 2025;16:9448. doi: 10.1038/s41467-025-64486-9. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R34] 34.Popov LD. Mitochondrial biogenesis: An update. J Cell Mol Med 2020;24:4892-4899. doi: 10.1111/jcmm.15194. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R35] 35.Hood DA, Memme JM, Oliveira AN, Moradi N, Champsi S. Mitochondrial biogenesis in skeletal muscle. Adv Exp Med Biol 2025;1478:19-50. doi: 10.1007/978-3-031-88361-3_2. [DOI] [PubMed] [Google Scholar]

[R36] 36.Horten P, Colina-Tenorio L, Rampelt H. Biogenesis of mitochondrial metabolite carriers. Biomolecules 2020;10:1008. doi: 10.3390/biom10071008. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R37] 37.Brischigliaro M, Sierra-Magro A, Ahn A, Barrientos A. Mitochondrial ribosome biogenesis and redox sensing. FEBS Open Bio 2024;14:1640-1655. doi: 10.1002/2211-5463.13844. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R38] 38.Cardanho-Ramos C, Morais VA. Mitochondrial biogenesis in neurons: How and where. Int J Mol Sci 2021;22:13059. doi: 10.3390/ijms222313059. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R39] 39.Chen D, Guo J, Li L. Catalpol promotes mitochondrial biogenesis in chondrocytes. Arch Physiol Biochem 2022;128:802-808. doi: 10.1080/13813455.2020.1727927. [DOI] [PubMed] [Google Scholar]

[R40] 40.Ren P, Gong F, Chang L, Hong X, Xing L, Zhang H. Zafirlukast promotes mitochondrial respiration by stimulating mitochondrial biogenesis in human bronchial epithelial cells. J Mol Histol 2021;52:643-650. doi: 10.1007/s10735-021-09974-0. [DOI] [PubMed] [Google Scholar]

[R41] 41.Kageyama M, Ito J, Shirasuna K, Kuwayama T, Iwata H. Mitochondrial reactive oxygen species regulate mitochondrial biogenesis in porcine embryos. J Reprod Dev 2021;67:141-147. doi: 10.1262/jrd.2020-111. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R42] 42.Liu L, Li Y, Chen G, Chen Q. Crosstalk between mitochondrial biogenesis and mitophagy to maintain mitochondrial homeostasis. J Biomed Sci 2023;30:86. doi: 10.1186/s12929-023-00975-7. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R43] 43.Daskalaki I, Tavernarakis N. Mitochondrial biogenesis in organismal senescence and neurodegeneration. Mech Ageing Dev 2020;191:111345. doi: 10.1016/j.mad.2020.111345. [DOI] [PubMed] [Google Scholar]

[R44] 44.Singh S, Singh RK. Recent advancements in the understanding of the alterations in mitochondrial biogenesis in Alzheimer’s disease. Mol Biol Rep 2025;52:173. doi: 10.1007/s11033-025-10297-6. [DOI] [PubMed] [Google Scholar]

[R45] 45.Kumar M Acevedo-Cintron J Jhaldiyal A Wang H Andrabi SA Eacker S, et al. Defects in mitochondrial biogenesis drive mitochondrial alterations in parkin-deficient human dopamine neurons. Stem Cell Reports 2020;15:629-645. doi: 10.1016/j.stemcr.2020.07.013. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R46] 46.Wang H Chen R Xiao L Kumar M Acevedo-Cintron J Siuda J, et al. Defects in mitochondrial biogenesis drive mitochondrial alterations in PINK1-deficient human dopamine neurons. bioRxiv 2023. doi: 10.1101/2023.06.23.546087. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R47] 47.Han X Zhang M Daowei L Liu L Ma X Xiong Y, et al. PGC-1 alpha regulates mitochondrial biogenesis to promote silica-induced pulmonary fibrosis. Toxicol Res (Camb) 2025;14:tfaf070. doi: 10.1093/toxres/tfaf070. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R48] 48.Hwang JH Kim KM Oh HT Yoo GD Jeong MG Lee H, et al. TAZ links exercise to mitochondrial biogenesis via mitochondrial transcription factor A. Nat Commun 2022;13:653. doi: 10.1038/s41467-022-28247-2. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R49] 49.Oliveira AN, Richards BJ, Slavin M, Hood DA. Exercise is muscle mitochondrial medicine. Exerc Sport Sci Rev 2021;49:67-76. doi: 10.1249/JES.0000000000000250. [DOI] [PubMed] [Google Scholar]

[R50] 50.Chodari L Dilsiz Aytemir M Vahedi P Alipour M Vahed SZ Khatibi SMH, et al. Targeting mitochondrial biogenesis with polyphenol compounds. Oxid Med Cell Longev 2021;2021:4946711. doi: 10.1155/2021/4946711. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R51] 51.Hinkle JS, Rivera CN, Vaughan RA. Branched-chain amino acids and mitochondrial biogenesis: An overview and mechanistic summary. Mol Nutr Food Res 2022;66:e2200109. doi: 10.1002/mnfr.202200109. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R52] 52.Alzhrani RF, Alhowyan AA, Taha EI, Attia SM, Salama SA, Harisa GI. Medication targeting to subcellular organelles: Emphasizing mitochondria as a therapeutic marvel-Current situation and future prospects. Exp Cell Res 2025;450:114647. doi: 10.1016/j.yexcr.2025.114647. [DOI] [PubMed] [Google Scholar]

[R53] 53.Green A, Hossain T, Eckmann DM. Mitochondrial dynamics involves molecular and mechanical events in motility, fusion and fission. Front Cell Dev Biol 2022;10:1010232. doi: 10.3389/fcell.2022.1010232. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R54] 54.Al Ojaimi M, Salah A, El-Hattab AW. Mitochondrial fission and fusion: Molecular mechanisms, biological functions, and related disorders. Membranes (Basel) 2022;12:893. doi: 10.3390/membranes12090893. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R55] 55.Adebayo M, Singh S, Singh AP, Dasgupta S. Mitochondrial fusion and fission: The fine-tune balance for cellular homeostasis. FASEB J 2021;35:e21620. doi: 10.1096/fj.202100067R. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R56] 56.Wisniewski BT, Lackner LL. Significantly reduced, but balanced, rates of mitochondrial fission and fusion are sufficient to maintain the integrity of yeast mitochondrial DNA. bioRxiv 2024:2024.07.18.604121. doi: 10.1101/2024.07.18.604121. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R57] 57.Wisniewski BT, Casler JC, Lackner LL. Significantly reduced, but balanced, rates of mitochondrial fission and fusion are sufficient to maintain the integrity of yeast mitochondrial DNA. Mol Biol Cell 2024;35:br25. doi: 10.1091/mbc.E24-07-0306. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R58] 58.Gu H, Yang K, Wu Q, Shen Z, Li X, Sun C. A link between protein acetylation and mitochondrial dynamics under energy metabolism: A comprehensive overview. J Cell Physiol 2021;236:7926-7937. doi: 10.1002/jcp.30461. [DOI] [PubMed] [Google Scholar]

[R59] 59.Uddin GM, Abbas R, Shutt TE. The role of protein acetylation in regulating mitochondrial fusion and fission. Biochem Soc Trans 2021;49:2807-2819. doi: 10.1042/BST20210798. [DOI] [PubMed] [Google Scholar]

[R60] 60.Wu Z, Xiao C, Li F, Huang W, You F, Li X. Mitochondrial fusion-fission dynamics and its involvement in colorectal cancer. Mol Oncol 2024;18:1058-1075. doi: 10.1002/1878-0261.13578. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R61] 61.Wu Z, Xiao C, Long J, Huang W, You F, Li X. Mitochondrial dynamics and colorectal cancer biology: Mechanisms and potential targets. Cell Commun Signal 2024;22:91. doi: 10.1186/s12964-024-01490-4. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R62] 62.Ren L, Chen X, Chen X, Li J, Cheng B, Xia J. Mitochondrial dynamics: Fission and fusion in fate determination of mesenchymal stem cells. Front Cell Dev Biol 2020;8:580070. doi: 10.3389/fcell.2020.580070. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R63] 63.Grel H Woznica D Ratajczak K Kalwarczyk E Anchimowicz J Switlik W, et al. Mitochondrial dynamics in neurodegenerative diseases: Unraveling the role of fusion and fission processes. Int J Mol Sci 2023;24:13033. doi: 10.3390/ijms241713033. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R64] 64.Liu X, Guo C, Zhang Q. Novel insights into the involvement of mitochondrial fission/fusion in heart failure: From molecular mechanisms to targeted therapies. Cell Stress Chaperones 2023;28:133-144. doi: 10.1007/s12192-023-01321-4. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R65] 65.Liu X, Li T, Tu X, Xu M, Wang J. Mitochondrial fission and fusion in neurodegenerative diseases: Ca(2+) signalling. Mol Cell Neurosci 2025;132:103992. doi: 10.1016/j.mcn.2025.103992. [DOI] [PubMed] [Google Scholar]

[R66] 66.Yu R Liu T Jin SB Ankarcrona M Lendahl U Nister M, et al. MIEF1/2 orchestrate mitochondrial dynamics through direct engagement with both the fission and fusion machineries. BMC Biol 2021;19:229. doi: 10.1186/s12915-021-01161-7. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R67] 67.Tran DT Tu Z Alawieh A Mulligan J Esckilsen S Quinn K, et al. Modulating donor mitochondrial fusion/fission delivers immunoprotective effects in cardiac transplantation. Am J Transplant 2022;22:386-401. doi: 10.1111/ajt.16882. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R68] 68.Fang Y, Min S, Shen H. The role of mitochondrial fusion and fission in immune-mediated inflammatory diseases. Cell Immunol 2024;403–404:104864. doi: 10.1016/j.cellimm.2024.104864. [DOI] [PubMed] [Google Scholar]

[R69] 69.Iqbal U, Malik A, Ibrahim L, Sial NT, Mehmood MH. Natural and synthetic potential drug leads for rheumatoid arthritis probing innovative target: Mitochondrial dysfunction and NLRP3 inflammasome activation. Naunyn Schmiedebergs Arch Pharmacol 2025;398:8295-8312. doi: 10.1007/s00210-025-03897-3. [DOI] [PubMed] [Google Scholar]

[R70] 70.Li P Wang G Peng Z Zhang L Yang F Wei Y, et al. The role of mitochondrial regulation in macrophage polarization: Implications for the pathogenesis of rheumatoid arthritis. J Inflamm Res 2025;18:17163-17183. doi: 10.2147/JIR.S560635. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R71] 71.Chen S Liu X Zhang W Li B Liu F Zhang Y, et al. Nanozyme coating-mediated mitochondrial metabolic reprogramming of macrophages for immunomodulatory osseointegration in rheumatoid arthritis case. ACS Nano 2025;19:26127-26146. doi: 10.1021/acsnano.5c07535. [DOI] [PubMed] [Google Scholar]

[R72] 72.Jiang X Lu Z Zhang Q Yu J Han D Liu J, et al. Osthole: A potential AMPK agonist that inhibits NLRP3 inflammasome activation by regulating mitochondrial homeostasis for combating rheumatoid arthritis. Phytomedicine 2023;110:154640. doi: 10.1016/j.phymed.2022.154640. [DOI] [PubMed] [Google Scholar]

[R73] 73.Wang S Zhao H Lin S Lv Y Lin Y Liu Y, et al. New therapeutic directions in type II diabetes and its complications: Mitochondrial dynamics. Front Endocrinol (Lausanne) 2023;14:1230168. doi: 10.3389/fendo.2023.1230168. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R74] 74.Narendra DP, Youle RJ. The role of PINK1-Parkin in mitochondrial quality control. Nat Cell Biol 2024;26:1639-1651. doi: 10.1038/s41556-024-01513-9. [DOI] [PubMed] [Google Scholar]

[R75] 75.Basak B, Holzbaur ELF. Mitophagy in neurons: Mechanisms regulating mitochondrial turnover and neuronal homeostasis. J Mol Biol 2025;437:169161. doi: 10.1016/j.jmb.2025.169161. [DOI] [PubMed] [Google Scholar]

[R76] 76.Chandra S, Katiyar P, Durairaj AS, Wang X. Mitochondrial calcium transport during autophagy initiation. Mitochondrial Commun 2024;2:14-20. doi: 10.1016/j.mitoco.2024.01.002. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R77] 77.Wu D, Ji H, Du W, Ren L, Qian G. Mitophagy alleviates ischemia/reperfusion-induced microvascular damage through improving mitochondrial quality control. Bioengineered 2022;13:3596-3607. doi: 10.1080/21655979.2022.2027065. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R78] 78.Fu T, Ma Y, Li Y, Wang Y, Wang Q, Tong Y. Mitophagy as a mitochondrial quality control mechanism in myocardial ischemic stress: From bench to bedside. Cell Stress Chaperones 2023;28:239-251. doi: 10.1007/s12192-023-01346-9. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R79] 79.Picca A, Calvani R, Coelho-Junior HJ, Marzetti E. Mitophagy: At the heart of mitochondrial quality control in cardiac aging and frailty. Exp Gerontol 2021;153:111508. doi: 10.1016/j.exger.2021.111508. [DOI] [PubMed] [Google Scholar]

[R80] 80.Tang Y, Xu W, Liu Y, Zhou J, Cui K, Chen Y. Autophagy protects mitochondrial health in heart failure. Heart Fail Rev 2024;29:113-123. doi: 10.1007/s10741-023-10354-x. [DOI] [PubMed] [Google Scholar]

[R81] 81.Song Y Xu Y Liu Y Gao J Feng L Zhang Y, et al. Mitochondrial quality control in the maintenance of cardiovascular homeostasis: The roles and interregulation of ups, mitochondrial dynamics and mitophagy. Oxid Med Cell Longev 2021;2021:3960773. doi: 10.1155/2021/3960773. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R82] 82.Haeussler S Kohler F Witting M Premm MF Rolland SG Fischer C, et al. Autophagy compensates for defects in mitochondrial dynamics. PLoS Genet 2020;16:e1008638. doi: 10.1371/journal.pgen.1008638. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R83] 83.Braun MM, Puglielli L. Defective PTEN-induced kinase 1/Parkin mediated mitophagy and neurodegenerative diseases. Front Cell Neurosci 2022;16:1031153. doi: 10.3389/fncel.2022.1031153. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R84] 84.Dernie F. Mitophagy in Parkinson’s disease: From pathogenesis to treatment target. Neurochem Int 2020;138:104756. doi: 10.1016/j.neuint.2020.104756. [DOI] [PubMed] [Google Scholar]

[R85] 85.Cen X, Zhang M, Zhou M, Ye L, Xia H. Mitophagy regulates neurodegenerative diseases. Cells 2021;10:1876. doi: 10.3390/cells10081876. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R86] 86.Cai Q, Jeong YY. Mitophagy in Alzheimer’s disease and other age-related neurodegenerative diseases. Cells 2020;9:150. doi: 10.3390/cells9010150. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R87] 87.Banarase TA Sammeta SS Wankhede NL Mangrulkar SV Rahangdale SR Aglawe MM, et al. Mitophagy regulation in aging and neurodegenerative disease. Biophys Rev 2023;15:239-255. doi: 10.1007/s12551-023-01057-6. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R88] 88.Yuk JM, Silwal P, Jo EK. Inflammasome and mitophagy connection in health and disease. Int J Mol Sci 2020;21:4714. doi: 10.3390/ijms21134714. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R89] 89.Mauri S, Favaro M, Bernardo G, Mazzotta GM, Ziviani E. Mitochondrial autophagy in the sleeping brain. Front Cell Dev Biol 2022;10:956394. doi: 10.3389/fcell.2022.956394. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R90] 90.Bakula D, Scheibye-Knudsen M. MitophAging: Mitophagy in aging and disease. Front Cell Dev Biol 2020;8:239. doi: 10.3389/fcell.2020.00239. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R91] 91.Zeng Z, Liang J, Wu L, Zhang H, Lv J, Chen N. Exercise-induced autophagy suppresses sarcopenia through Akt/mTOR and Akt/FoxO3a signal pathways and AMPK-mediated mitochondrial quality control. Front Physiol 2020;11:583478. doi: 10.3389/fphys.2020.583478. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R92] 92.Gomora-Garcia JC Montiel T Huttenrauch M Salcido-Gomez A Garcia-Velazquez L Ramiro-Cortes Y, et al. Effect of the ketone body, D-beta-hydroxybutyrate, on sirtuin2-mediated regulation of mitochondrial quality control and the autophagy-lysosomal pathway. Cells 2023;12:486. doi: 10.3390/cells12030486. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R93] 93.Liu Z Qin G Yang J Wang W Zhang W Lu B, et al. Targeting mitochondrial degradation by chimeric autophagy-tethering compounds. Chem Sci 2023;14:11192-11202. doi: 10.1039/d3sc03600f. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R94] 94.Kim JS, Chapman WC, Lin Y. Mitochondrial autophagy in ischemic aged livers. Cells 2022;11:4083. doi: 10.3390/cells11244083. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R95] 95.Wang C, Wang Y. The role and mechanism of action of mitophagy in various liver diseases. Antioxid Redox Signal 2023;38:529-549. doi: 10.1089/ars.2022.0114. [DOI] [PubMed] [Google Scholar]

[R96] 96.Dantas WS Zunica ERM Heintz EC Vandanmagsar B Floyd ZE Yu Y, et al. Mitochondrial uncoupling attenuates sarcopenic obesity by enhancing skeletal muscle mitophagy and quality control. J Cachexia Sarcopenia Muscle 2022;13:1821-1836. doi: 10.1002/jcsm.12982. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R97] 97.Hou GZ, Guo Q, Han PP. Autophagy activation and mitochondrial quality control in sarcopenia (in Chinese). Acta Academiae Medicinae Sinicae 2022;44:709-716. doi: 10.3881/j.issn.1000-503X.13753. [DOI] [PubMed] [Google Scholar]

[R98] 98.Liu M Chen J Sun M Zhang L Yu Y Mi W, et al. Protection of Ndrg2 deficiency on renal ischemia-reperfusion injury via activating PINK1/Parkin-mediated mitophagy. Chin Med J 2024;137:2603-2614. doi: 10.1097/CM9.0000000000002957. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R99] 99.Tang X Zhang A Feng X Wang W Chen F Tao Y, et al. Global research trends on the associations between chronic kidney disease and mitochondria: Insights from the bibliometric analysis. Int Urol Nephrol 2025;57:2579-2594. doi: 10.1007/s11255-025-04437-x. [DOI] [PubMed] [Google Scholar]

[R100] 100.Wei X Wang Y Lao Y Weng J Deng R Li S, et al. Effects of honokiol protects against chronic kidney disease via BNIP3/NIX and FUNDC1-mediated mitophagy and AMPK pathways. Mol Biol Rep 2023;50:6557-6568. doi: 10.1007/s11033-023-08592-1. [DOI] [PubMed] [Google Scholar]

[R101] 101.Aranda-Rivera AK Amador-Martinez I Aparicio-Trejo OE Leon-Contreras JC Hernandez-Pando R Saavedra E, et al. Sulforaphane restores mitochondrial beta-oxidation and reduces renal lipid accumulation in a model of releasing unilateral ureteral obstruction. Antioxidants (Basel) 2025;14:288. doi: 10.3390/antiox14030288. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R102] 102.Jia Q Han L Zhang X Yang W Gao Y Shen Y, et al. Tongluo yishen decoction ameliorates renal fibrosis via regulating mitochondrial dysfunction induced by oxidative stress in unilateral ureteral obstruction rats. Front Pharmacol 2021;12:762756. doi: 10.3389/fphar.2021.762756. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R103] 103.Wu Y Yang F Zhou G Wang Q Xing C Bai H, et al. Molybdenum and cadmium co-induce mitochondrial quality control disorder via FUNDC1-mediated mitophagy in sheep kidney. Front Vet Sci 2022;9:842259. doi: 10.3389/fvets.2022.842259. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R104] 104.Wang L Duan Z Liang M Wang C Liang T Sun L, et al. A pivotal role of selective autophagy in mitochondrial quality control: Implications for zinc oxide nanoparticles induced neurotoxicity. Chem Biol Interact 2022;363:110003. doi: 10.1016/j.cbi.2022.110003. [DOI] [PubMed] [Google Scholar]

[R105] 105.Javaid HMA, Lim H, Shin S, Huh JY. Inhibition of autophagy with chloroquine dysregulates mitochondrial quality control and energetics in adipocytes. Arch Pharm Res 2022;45:731-742. doi: 10.1007/s12272-022-01412-3. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R106] 106.Sasaki Y, Ikeda Y, Uchikado Y, Akasaki Y, Sadoshima J, Ohishi M. Estrogen plays a crucial role in Rab9-dependent mitochondrial autophagy, delaying arterial senescence. J Am Heart Assoc 2021;10:e019310. doi: 10.1161/JAHA.120.019310. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R107] 107.Xu Z Fu T Guo Q Zhou D Sun W Zhou Z, et al. Disuse-associated loss of the protease LONP1 in muscle impairs mitochondrial function and causes reduced skeletal muscle mass and strength. Nat Commun 2022;13:894. doi: 10.1038/s41467-022-28557-5. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R108] 108.Uchikado Y, Ikeda Y, Sasaki Y, Iwabayashi M, Akasaki Y, Ohishi M. Association of Lectin-like oxidized low-density lipoprotein receptor-1 with angiotensin II type 1 receptor impacts mitochondrial quality control, offering promise for the treatment of vascular senescence. Front Cardiovasc Med 2021;8:788655. doi: 10.3389/fcvm.2021.788655. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R109] 109.Towers CG, Wodetzki DK, Thorburn J, Smith KR, Caino MC, Thorburn A. Mitochondrial-derived vesicles compensate for loss of LC3-mediated mitophagy. Dev Cell 2021;56:2029-2042.e25. doi: 10.1016/j.devcel.2021.06.003. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R110] 110.Shin CS Meng S Garbis SD Moradian A Taylor RW Sweredoski MJ, et al. LONP1 and mtHSP70 cooperate to promote mitochondrial protein folding. Nat Commun 2021;12:265. doi: 10.1038/s41467-020-20597-z. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R111] 111.Kan KT, Wilcock J, Lu H. Role of Yme1 in mitochondrial protein homeostasis: From regulation of protein import, OXPHOS function to lipid synthesis and mitochondrial dynamics. Biochem Soc Trans 2024;52:1539-1548. doi: 10.1042/BST20240450. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R112] 112.Li J Zhu J Deng Y Reck EC Walker EM Sidarala V, et al. LONP1 regulation of mitochondrial protein folding provides insight into beta cell failure in type 2 diabetes. bioRxiv 2024;2024.06.03.597215. doi: 10.1101/2024.06.03.597215. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R113] 113.Rolland S, Conradt B. Genetic screen identifies non-mitochondrial proteins involved in the maintenance of mitochondrial homeostasis. MicroPubl Biol 2022;2022:10.17912/micropub.biology.000562. doi: 10.17912/micropub.biology.000562. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R114] 114.Cilleros-Holgado P Gomez-Fernandez D Pinero-Perez R Romero-Dominguez JM Reche-Lopez D Lopez-Cabrera A, et al. Mitochondrial quality control via mitochondrial unfolded protein response (mtUPR) in ageing and neurodegenerative diseases. Biomolecules 2023;13:1789. doi: 10.3390/biom13121789. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R115] 115.Yang M Luo S Chen W He L Liu D Wang X, et al. Mitochondrial unfolded protein response (mtUPR) and diseases. Curr Med Chem 2025;32:1674-1684. doi: 10.2174/0929867331666230822095924. [DOI] [PubMed] [Google Scholar]

[R116] 116.Haynes CM, Hekimi S. Mitochondrial dysfunction, aging, and the mitochondrial unfolded protein response in Caenorhabditis elegans. Genetics 2022;222:iyac160. doi: 10.1093/genetics/iyac160. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R117] 117.Zhou Z Lu J Yang M Cai J Fu Q Ma J, et al. The mitochondrial unfolded protein response (UPR(mt)) protects against osteoarthritis. Exp Mol Med 2022;54:1979-1990. doi: 10.1038/s12276-022-00885-y. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R118] 118.Deng J Wang D Shi Y Lin L Gao W Sun Y, et al. Mitochondrial unfolded protein response mechanism and its cardiovascular protective effects. Biomed Pharmacother 2024;177:116989. doi: 10.1016/j.biopha.2024.116989. [DOI] [PubMed] [Google Scholar]

[R119] 119.Maruszczak KK, Ayyamperumal S, Chacinska A. Defective mitochondrial import as a challenge for cellular protein homeostasis. FEBS Lett 2023;597:1555-1568. doi: 10.1002/1873-3468.14677. [DOI] [PubMed] [Google Scholar]

[R120] 120.Lee-Glover LP, Shutt TE. Mitochondrial quality control pathways sense mitochondrial protein import. Trends Endocrinol Metab 2024;35:308-320. doi: 10.1016/j.tem.2023.11.004. [DOI] [PubMed] [Google Scholar]

[R121] 121.Balzarini M, Kim J, Weidberg H. Quality control of un-imported mitochondrial proteins at a glance. J Cell Sci 2025;138:jcs263757. doi: 10.1242/jcs.263757. [DOI] [PubMed] [Google Scholar]

[R122] 122.Hu L Li J Guo H Su L Dong P Huang J, et al. SENP6 maintains mitochondrial homeostasis by regulating mitochondrial protein import through deSUMOylation of TOM40. Adv Sci (Weinh) 2025;12:e03408. doi: 10.1002/advs.202503408. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R123] 123.Nowicka U Chroscicki P Stroobants K Sladowska M Turek M Uszczynska-Ratajczak B, et al. Cytosolic aggregation of mitochondrial proteins disrupts cellular homeostasis by stimulating the aggregation of other proteins. eLife 2021;10:e65484. doi: 10.7554/eLife.65484. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R124] 124.Jenkins EC, Chattopadhyay M, Germain D. Folding mitochondrial-mediated cytosolic proteostasis into the mitochondrial unfolded protein response. Front Cell Dev Biol 2021;9:715923. doi: 10.3389/fcell.2021.715923. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R125] 125.Felipe Perez R, Mochi G, Khan A, Woodford M. Mitochondrial chaperone code: Just warming up. Cell Stress Chaperones 2024;29:483-496. doi: 10.1016/j.cstres.2024.05.002. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R126] 126.Konovalova S Torregrosa-Munumer R Manjunath P Liu X Baral S Fatima K, et al. Small mitochondrial protein NERCLIN regulates cardiolipin homeostasis and mitochondrial ultrastructure. Proc Natl Acad Sci U S A 2023;120:e2210599120. doi: 10.1073/pnas.2210599120. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R127] 127.Wachoski-Dark E, Zhao T, Khan A, Shutt TE, Greenway SC. Mitochondrial protein homeostasis and cardiomyopathy. Int J Mol Sci 2022;23:3353. doi: 10.3390/ijms23063353. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R128] 128.Zhao T Goedhart C Pfeffer G Greenway SC Lines M Khan A, et al. Skeletal phenotypes due to abnormalities in mitochondrial protein homeostasis and import. Int J Mol Sci 2020;21:8327. doi: 10.3390/ijms21218327. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R129] 129.Jishi A, Qi X. Altered mitochondrial protein homeostasis and proteinopathies. Front Mol Neurosci 2022;15:867935. doi: 10.3389/fnmol.2022.867935. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R130] 130.Jagtap YA Kumar P Kinger S Dubey AR Choudhary A Gutti RK, et al. Disturb mitochondrial associated proteostasis: Neurodegeneration and imperfect ageing. Front Cell Dev Biol 2023;11:1146564. doi: 10.3389/fcell.2023.1146564. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R131] 131.Guo J Wang Y Zhang D Shi C Zhang X Li X, et al. The FMO3/TMAO/HSP90beta axis aggravates MAFLD by disrupting mitochondrial protein homeostasis. Cell Signal 2025;134:111960. doi: 10.1016/j.cellsig.2025.111960. [DOI] [PubMed] [Google Scholar]

[R132] 132.Lima TI Laurila PP Wohlwend M Morel JD Goeminne LJE Li H, et al. Inhibiting de novo ceramide synthesis restores mitochondrial and protein homeostasis in muscle aging. Sci Transl Med 2023;15:eade6509. doi: 10.1126/scitranslmed.ade6509. [DOI] [PubMed] [Google Scholar]

[R133] 133.Molenaars M, Daniels EG, Meurs A, Janssens GE, Houtkooper RH. Mitochondrial cross-compartmental signalling to maintain proteostasis and longevity. Philos Trans R Soc Lond B Biol Sci 2020;375:20190414. doi: 10.1098/rstb.2019.0414. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R134] 134.Baker MJ, Yek KQ, Stojanovski D. Quality control at the powerhouse: Mitochondrial proteostasis dysfunction and disease. Biochem Soc Trans 2025;53:1-13. doi: 10.1042/BST20253044. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R135] 135.Madrazo N, Khattar Z, Powers ET, Rosarda JD, Wiseman RL. Mapping stress-responsive signaling pathways induced by mitochondrial proteostasis perturbations. Mol Biol Cell 2024;35:ar74. doi: 10.1091/mbc.E24-01-0041. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R136] 136.Popov LD. Mitochondrial-derived vesicles: Recent insights. J Cell Mol Med 2022;26:3323-3328. doi: 10.1111/jcmm.17391. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R137] 137.Peng T, Xie Y, Sheng H, Wang C, Lian Y, Xie N. Mitochondrial-derived vesicles: Gatekeepers of mitochondrial response to oxidative stress. Free Radic Biol Med 2022;188:185-193. doi: 10.1016/j.freeradbiomed.2022.06.233. [DOI] [PubMed] [Google Scholar]

[R138] 138.Tang M Tu Y Gong Y Yang Q Wang J Zhang Z, et al. Beta-hydroxybutyrate facilitates mitochondrial-derived vesicle biogenesis and improves mitochondrial functions. Mol Cell 2025;85:1395-1410.e95. doi: 10.1016/j.molcel.2025.02.022. [DOI] [PubMed] [Google Scholar]

[R139] 139.Sekine S, Sekine Y. Metabolite tunes MDV pathway to maintain mitochondrial fitness. Mol Cell 2025;85:1253-1255. doi: 10.1016/j.molcel.2025.02.027. [DOI] [PubMed] [Google Scholar]

[R140] 140.Bao F, Zeng D, Xiao J, Zhou L, Liu X. Beta-hydroxybutyrate enhances mitochondrial function via mitochondrial-derived vesicles. Sci Bull (Beijing) 2025;70:3100-3102. doi: 10.1016/j.scib.2025.05.011. [DOI] [PubMed] [Google Scholar]

[R141] 141.Konig T Nolte H Aaltonen MJ Tatsuta T Krols M Stroh T, et al. MIROs and DRP1 drive mitochondrial-derived vesicle biogenesis and promote quality control. Nat Cell Biol 2021;23:1271-1286. doi: 10.1038/s41556-021-00798-4. [DOI] [PubMed] [Google Scholar]

[R142] 142.Konig T, McBride HM. Mitochondrial-derived vesicles in metabolism, disease, and aging. Cell Metab 2024;36:21-35. doi: 10.1016/j.cmet.2023.11.014. [DOI] [PubMed] [Google Scholar]

[R143] 143.Ryan TA Phillips EO Collier CL Jb Robinson A Routledge D Wood RE, et al. Tollip coordinates Parkin-dependent trafficking of mitochondrial-derived vesicles. EMBO J 2020;39:e102539. doi: 10.15252/embj.2019102539. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R144] 144.Mondal P, Towers C. Beyond mitophagy: Mitochondrial-derived vesicles can get the job done! Autophagy 2022;18:449-451. doi: 10.1080/15548627.2021.1999562. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R145] 145.Li B Zhao H Wu Y Zhu Y Zhang J Yang G, et al. Mitochondrial-derived vesicles protect cardiomyocytes against hypoxic damage. Front Cell Dev Biol 2020;8:214. doi: 10.3389/fcell.2020.00214. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R146] 146.Heyn J, Heuschkel MA, Goettsch C. Mitochondrial-derived vesicles-link to extracellular vesicles and implications in cardiovascular disease. Int J Mol Sci 2023;24:3100-3102. doi: 10.3390/ijms24032637. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R147] 147.Kong J Sun R Du C Tang Y Xie C Li Q, et al. Mitochondrial extracellular vesicles: A novel approach to mitochondrial quality control. Biomolecules 2025;15:1145. doi: 10.3390/biom15081145. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R148] 148.Iorio R, Petricca S, Di Emidio G, Falone S, Tatone C. Mitochondrial extracellular vesicles (mitoEVs): Emerging mediators of cell-to-cell communication in health, aging and age-related diseases. Ageing Res Rev 2024;101:102522. doi: 10.1016/j.arr.2024.102522. [DOI] [PubMed] [Google Scholar]

[R149] 149.Allan HE Dark N Vulliamy P Crescente M Maffucci T Armstrong PC, et al. Platelet mitochondrial transfer via extracellular vesicles modulates neutrophil phenotype and function. J Thromb Haemost 2025;23:3665-3677. doi: 10.1016/j.jtha.2025.08.004. [DOI] [PubMed] [Google Scholar]

[R150] 150.Ferrucci L, Guerra F, Bucci C, Marzetti E, Picca A. Mitochondria break free: Mitochondria-derived vesicles in aging and associated conditions. Ageing Res Rev 2024;102:102549. doi: 10.1016/j.arr.2024.102549. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R151] 151.Hong WL, Huang H, Zeng X, Duan CY. Targeting mitochondrial quality control: New therapeutic strategies for major diseases. Mil Med Res 2024;11:59. doi: 10.1186/s40779-024-00556-1. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R152] 152.Beatriz M Vilaca R Anjo SI Manadas B Januario C Rego AC, et al. Defective mitochondria-lysosomal axis enhances the release of extracellular vesicles containing mitochondrial DNA and proteins in Huntington’s disease. J Extracell Biol 2022;1:e65. doi: 10.1002/jex2.65. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R153] 153.Garesse R, Vallejo CG. Animal mitochondrial biogenesis and function: A regulatory cross-talk between two genomes. Gene 2001;263:1-16. doi: 10.1016/s0378-1119(00)00582-5. [DOI] [PubMed] [Google Scholar]

[R154] 154.Allkanjari K, Baldock RA. Beyond base excision repair: An evolving picture of mitochondrial DNA repair. Biosci Rep 2021;41:BSR20211320. doi: 10.1042/BSR20211320. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R155] 155.LeDoux SP, Druzhyna NM, Hollensworth SB, Harrison JF, Wilson GL. Mitochondrial DNA repair: A critical player in the response of cells of the CNS to genotoxic insults. Neuroscience 2007;145:1249-1259. doi: 10.1016/j.neuroscience.2006.10.002. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R156] 156.Lu J, Li Y, Mollinari C, Garaci E, Merlo D, Pei G. Amyloid-beta oligomers-induced mitochondrial DNA repair impairment contributes to altered human neural stem cell differentiation. Curr Alzheimer Res 2019;16:934-949. doi: 10.2174/1567205016666191023104036. [DOI] [PubMed] [Google Scholar]

[R157] 157.Ngo HB, Lovely GA, Phillips R, Chan DC. Distinct structural features of TFAM drive mitochondrial DNA packaging versus transcriptional activation. Nat Commun 2014;5:3077. doi: 10.1038/ncomms4077. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R158] 158.Frandsen JR Yuan Z Bedi B Prasla Z Choi SR Narayanasamy P, et al. PGC-1alpha activation to enhance macrophage immune function in mycobacterial infections. PLoS One 2025;20:e0310908. doi: 10.1371/journal.pone.0310908. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R159] 159.Kumagai H Miller B Kim SJ Leelaprachakul N Kikuchi N Yen K, et al. Novel insights into mitochondrial DNA: Mitochondrial microproteins and mtDNA variants modulate athletic performance and age-related diseases. Genes (Basel) 2023;14:286. doi: 10.3390/genes14020286. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R160] 160.Lee C, Kim KH, Cohen P. MOTS-c: A novel mitochondrial-derived peptide regulating muscle and fat metabolism. Free Radic Biol Med 2016;100:182-187. doi: 10.1016/j.freeradbiomed.2016.05.015. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R161] 161.Chen S Bao X Chen H Jia M Li W Zhang L, et al. Thyroid cancer-associated mitochondrial DNA mutation G3842A promotes tumorigenicity via ROS-mediated ERK1/2 activation. Oxid Med Cell Longev 2022;2022:9982449. doi: 10.1155/2022/9982449. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R162] 162.Tsybrovskyy O De Luise M de Biase D Caporali L Fiorini C Gasparre G, et al. Papillary thyroid carcinoma tall cell variant shares accumulation of mitochondria, mitochondrial DNA mutations, and loss of oxidative phosphorylation complex I integrity with oncocytic tumors. J Pathol Clin Res 2022;8:155-168. doi: 10.1002/cjp2.247. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R163] 163.Kowluru RA, Kumar J, Malaviya P. DNA methylation of long noncoding RNA cytochrome B in diabetic retinopathy. Noncoding RNA Res 2025;11:141-149. doi: 10.1016/j.ncrna.2024.12.007. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R164] 164.Batsaikhan J Park KH Chang HR Jung E Kim MJ Kang J, et al. KU80 suppresses endonuclease G activity to preserve genomic integrity. FEBS J 2026. doi: 10.1111/febs.70495. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R165] 165.Feng Y, Lu Y. The nuclear-mitochondrial crosstalk in aging: From mechanisms to therapeutics. Free Radic Biol Med 2025;232:391-397. doi: 10.1016/j.freeradbiomed.2025.03.012. [DOI] [PubMed] [Google Scholar]

[R166] 166.Perez-Trevino P, Velasquez M, Garcia N. Mechanisms of mitochondrial DNA escape and its relationship with different metabolic diseases. Biochim Biophys Acta Mol Basis Dis 2020;1866:165761. doi: 10.1016/j.bbadis.2020.165761. [DOI] [PubMed] [Google Scholar]

[R167] 167.Saxena R de Bakker PI Singer K Mootha V Burtt N Hirschhorn JN, et al. Comprehensive association testing of common mitochondrial DNA variation in metabolic disease. Am J Hum Genet 2006;79:54-61. doi: 10.1086/504926. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R168] 168.Guo DF Merrill RA Qian L Hsu Y Zhang Q Lin Z, et al. The BBSome regulates mitochondria dynamics and function. Mol Metab 2023;67:101654. doi: 10.1016/j.molmet.2022.101654. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R169] 169.Jacob S Kosaka Y Bhatlekar S Denorme F Benzon H Moody A, et al. Mitofusin-2 regulates platelet mitochondria and function. Circ Res 2024;134:143-161. doi: 10.1161/CIRCRESAHA.123.322914. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R170] 170.Zhu R Liu L Mao T Wang X Li Y Li T, et al. Mfn2 regulates mitochondria and mitochondria-associated endoplasmic reticulum membrane function in neurodegeneration induced by repeated sevoflurane exposure. Exp Neurol 2024;377:114807. doi: 10.1016/j.expneurol.2024.114807. [DOI] [PubMed] [Google Scholar]

[R171] 171.Li Y Huang D Jia L Shangguan F Gong S Lan L, et al. LonP1 links mitochondria-ER interaction to regulate heart function. Research (Wash D C) 2023;6:0175. doi: 10.34133/research.0175. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R172] 172.Harada T Sada R Osugi Y Matsumoto S Matsuda T Hayashi-Nishino M, et al. Palmitoylated CKAP4 regulates mitochondrial functions through an interaction with VDAC2 at ER-mitochondria contact sites. J Cell Sci 2020;133:jcs249045. doi: 10.1242/jcs.249045. [DOI] [PubMed] [Google Scholar]

[R173] 173.Ravanelli S, den Brave F, Hoppe T. Mitochondrial quality control governed by ubiquitin. Front Cell Dev Biol 2020;8:270. doi: 10.3389/fcell.2020.00270. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R174] 174.Aphasizheva I, Aphasizhev R. Mitochondrial RNA quality control in trypanosomes. Wiley Interdiscip Rev RNA 2021;12:e1638. doi: 10.1002/wrna.1638. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R175] 175.Brzezniakiewicz-Janus K, Jarczak J, Konopko A, Ratajczak J, Kucia M, Ratajczak MZ. Mitochondria express functional signaling ligand-binding receptors that regulate their biological responses-The novel role of mitochondria as stress-response sentinels. Stem Cell Rev Rep 2025;21:597-604. doi: 10.1007/s12015-025-10847-2. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R176] 176.Wu X Yi X Zhao B Zhi Y Xu Z Cao Y, et al. The volume regulated anion channel VRAC regulates NLRP3 inflammasome by modulating itaconate efflux and mitochondria function. Pharmacol Res 2023;198:107016. doi: 10.1016/j.phrs.2023.107016. [DOI] [PubMed] [Google Scholar]

[R177] 177.Ledderose C, Junger WG. Mitochondria synergize with P2 receptors to regulate human T cell function. Front Immunol 2020;11:549889. doi: 10.3389/fimmu.2020.549889. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R178] 178.Wang ZH, Chen L, Li W, Chen L, Wang YP. Mitochondria transfer and transplantation in human health and diseases. Mitochondrion 2022;65:80-87. doi: 10.1016/j.mito.2022.05.002. [DOI] [PubMed] [Google Scholar]

[R179] 179.Dong LF Rohlena J Zobalova R Nahacka Z Rodriguez AM Berridge MV, et al. Mitochondria on the move: Horizontal mitochondrial transfer in disease and health. J Cell Biol 2023;222:e202211044. doi: 10.1083/jcb.202211044. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R180] 180.Feng H Tian C Jiang W Sun Z Li Y Han B, et al. Hydrogen sulfide sustains mitochondria functions via targeting mitochondria fission regulator 1 like protein to restore human cytotrophoblast invasion and migration. Int J Biol Macromol 2025;299:140240. doi: 10.1016/j.ijbiomac.2025.140240. [DOI] [PubMed] [Google Scholar]

[R181] 181.Zhou L, Wang Q. Advances of H(2)S in regulating neurodegenerative diseases by preserving mitochondria function. Antioxidants (Basel) 2023;12:652. doi: 10.3390/antiox12030652. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R182] 182.Ding Y Gui X Chu X Sun Y Zhang S Tong H, et al. MTH1 protects platelet mitochondria from oxidative damage and regulates platelet function and thrombosis. Nat Commun 2023;14:4829. doi: 10.1038/s41467-023-40600-7. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R183] 183.Ikeda T, Watanabe S, Mitani T. Genistein regulates adipogenesis by blocking the function of adenine nucleotide translocase-2 in the mitochondria. Biosci Biotechnol Biochem 2022;86:260-272. doi: 10.1093/bbb/zbab203. [DOI] [PubMed] [Google Scholar]

[R184] 184.Zhang MY, Zhang H, Yao YM, Yang DW. Kruppel-like factors in mitochondrial quality control. Front Physiol 2025;16:1554877. doi: 10.3389/fphys.2025.1554877. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R185] 185.Labbadia J. Potential roles for mitochondria-to-HSF1 signaling in health and disease. Front Mol Biosci 2023;10:1332658. doi: 10.3389/fmolb.2023.1332658. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R186] 186.Ye L, Fu X, Li Q. Mitochondrial quality control in health and disease. MedComm (2020) 2025;6:e70319. doi: 10.1002/mco2.70319. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R187] 187.Zheng Y Yang J Li X Qi L Zheng Z Kong J, et al. Mitochondria at the crossroads: Quality control mechanisms in neuronal senescence and neurodegeneration. Neurobiol Dis 2025;208:106862. doi: 10.1016/j.nbd.2025.106862. [DOI] [PubMed] [Google Scholar]

[R188] 188.Fan H He Z Huang H Zhuang H Liu H Liu X, et al. Mitochondrial quality control in cardiomyocytes: A critical role in the progression of cardiovascular diseases. Front Physiol 2020;11:252. doi: 10.3389/fphys.2020.00252. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R189] 189.Cheung C, Tu S, Feng Y, Wan C, Ai H, Chen Z. Mitochondrial quality control dysfunction in osteoarthritis: Mechanisms, therapeutic strategies and future prospects. Arch Gerontol Geriatr 2024;125:105522. doi: 10.1016/j.archger.2024.105522. [DOI] [PubMed] [Google Scholar]

[R190] 190.Pietrangelo D, Lopa C, Litterio M, Cotugno M, Rubattu S, Lombardi A. Metabolic disturbances involved in cardiovascular diseases: The role of mitochondrial dysfunction, altered bioenergetics and oxidative stress. Int J Mol Sci 2025;26:6791. doi: 10.3390/ijms26146791. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R191] 191.Wang Y, Liu HH, Cao YT, Zhang LL, Huang F, Yi C. The role of mitochondrial dynamics and mitophagy in carcinogenesis, metastasis and therapy. Front Cell Dev Biol 2020;8:413. doi: 10.3389/fcell.2020.00413. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R192] 192.Romanello V, Sandri M. Implications of mitochondrial fusion and fission in skeletal muscle mass and health. Semin Cell Dev Biol 2023;143:46-53. doi: 10.1016/j.semcdb.2022.02.011. [DOI] [PubMed] [Google Scholar]

[R193] 193.Kabra UD, Jastroch M. Mitochondrial dynamics and insulin secretion. Int J Mol Sci 2023;24:13782. doi: 10.3390/ijms241813782. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R194] 194.Zhang L, Wei Y, Yuan S, Sun L. Targeting mitochondrial metabolic reprogramming as a potential approach for cancer therapy. Int J Mol Sci 2023;24:4954. doi: 10.3390/ijms24054954. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R195] 195.Ruan P, Zheng Y, Dong Z, Wang Y, Xu Y, Chen H. Research progress in the regulation of autophagy and mitochondrial homeostasis by AMPK signaling channels (in Chinese). Chinese Critical Care Medicine 2024;36:425-429. doi: 10.3760/cma.j.cn121430-20230302-00132. [DOI] [PubMed] [Google Scholar]

[R196] 196.Ahmed Selim N, Wojtovich AP. Mitochondrial membrane potential and compartmentalized signaling: Calcium, ROS, and beyond. Redox Biol 2025;86:103859. doi: 10.1016/j.redox.2025.103859. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R197] 197.Zhang L Qi J Zhang X Zhao X An P Luo Y, et al. The regulatory roles of mitochondrial calcium and the mitochondrial calcium uniporter in tumor cells. Int J Mol Sci 2022;23:6667. doi: 10.3390/ijms23126667. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R198] 198.Chen L, Liu Y, Zhang J, Song T, Wu J, Ren Z. AMPK regulates ARF1 localization to membrane contact sites to facilitate fatty acid transfer between lipid droplets and mitochondria. Cell Death Dis 2025;16:623. doi: 10.1038/s41419-025-07957-7. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R199] 199.Li YE, Sowers JR, Hetz C, Ren J. Cell death regulation by MAMs: From molecular mechanisms to therapeutic implications in cardiovascular diseases. Cell Death Dis 2022;13:504. doi: 10.1038/s41419-022-04942-2. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R200] 200.Favorit V, Hood WR, Kavazis AN, Skibiel AL. Graduate student literature review: Mitochondrial adaptations across lactation and their molecular regulation in dairy cattle. J Dairy Sci 2021;104:10415-10425. doi: 10.3168/jds.2021-20138. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R201] 201.Song H Zhang X Wang J Wu Y Xiong T Shen J, et al. The regulatory role of adipocyte mitochondrial homeostasis in metabolism-related diseases. Front Physiol 2023;14:1261204. doi: 10.3389/fphys.2023.1261204. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R202] 202.Yu LP Li YQ Li YJ Zi L Tao YX Hao JJ, et al. In vivo identification of the pharmacodynamic ingredients of polygonum cuspidatum for remedying the mitochondria to alleviate metabolic dysfunction-associated fatty liver disease. Biomed Pharmacother 2022;156:113849. doi: 10.1016/j.biopha.2022.113849. [DOI] [PubMed] [Google Scholar]

[R203] 203.Shen X, Sun P, Zhang H, Yang H. Mitochondrial quality control in the brain: The physiological and pathological roles. Front Neurosci 2022;16:1075141. doi: 10.3389/fnins.2022.1075141. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R204] 204.Lei X Xu Z Huang L Huang Y Tu S Xu L, et al. The potential influence of melatonin on mitochondrial quality control: A review. Front Pharmacol 2023;14:1332567. doi: 10.3389/fphar.2023.1332567. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R205] 205.Stojakovic A Chang SY Nesbitt J Pichurin NP Ostroot MA Aikawa T, et al. Partial inhibition of mitochondrial complex I reduces tau pathology and improves energy homeostasis and synaptic function in 3xTg-AD mice. J Alzheimers Dis 2021;79:335-353. doi: 10.3233/JAD-201015. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R206] 206.Liu Y Fu T Li G Li B Luo G Li N, et al. Mitochondrial transfer between cell crosstalk-An emerging role in mitochondrial quality control. Ageing Res Rev 2023;91:102038. doi: 10.1016/j.arr.2023.102038. [DOI] [PubMed] [Google Scholar]

[R207] 207.Zhong Y Liu J Sun D Guo T Yao Y Xia X, et al. Dioscin relieves diabetic nephropathy via suppressing oxidative stress and apoptosis, and improving mitochondrial quality and quantity control. Food Funct 2022;13:3660-3673. doi: 10.1039/d1fo02733f. [DOI] [PubMed] [Google Scholar]

[R208] 208.Ma X Liu Y Ding B Liu Y Zhang Y Wang Y, et al. Blueberry anthocyanins ameliorate arsenic-induced cognitive impairment in rats: Mitigating mitochondrial damage and dysregulation. Phytomedicine 2025;145:157062. doi: 10.1016/j.phymed.2025.157062. [DOI] [PubMed] [Google Scholar]

[R209] 209.Tang H, Zheng Z, Wang H, Wang L, Zhao G, Wang P. Vitamin K2 modulates mitochondrial dysfunction induced by 6-hydroxydopamine in SH-SY5Y cells via mitochondrial quality-control loop. Nutrients 2022;14:1504. doi: 10.3390/nu14071504. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R210] 210.Ning X Tang J Li X Wang J Zhai F Jiang C, et al. Dexmedetomidine ameliorates hepatic ischemia reperfusion injury via modulating SIRT3 mediated mitochondrial quality control. Sci Rep 2025;15:5630. doi: 10.1038/s41598-025-90069-1. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R211] 211.Vandvali F, Kia HD, Najafi A, Rafieian-Naeini HR, Kim WK. Improving rooster semen cryopreservation with telmisartan-enhanced extender. Poult Sci 2025;104:104694. doi: 10.1016/j.psj.2024.104694. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R212] 212.Vandvali F, Kia HD, Ebrahimi M, Moghaddam G, Najafi A. Impact of losartan-supplemented extender on enhancing rooster sperm quality post-freezing and thawing. Poult Sci 2025;104:105179. doi: 10.1016/j.psj.2025.105179. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R213] 213.Kuzelova L Svoradova A Balazi A Vasicek J Langraf V Kolesarova A, et al. Enhancing of rabbit sperm cryopreservation with antioxidants mito-tempo and berberine. Antioxidants (Basel) 2024;13:1360. doi: 10.3390/antiox13111360. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R214] 214.He L, Liu F, Li J. Mitochondrial sirtuins and doxorubicin-induced cardiotoxicity. Cardiovasc Toxicol 2021;21:179-191. doi: 10.1007/s12012-020-09626-x. [DOI] [PubMed] [Google Scholar]

[R215] 215.Zhang P Lu H Wu Y Lu D Li C Yang X, et al. COX5A alleviates doxorubicin-induced cardiotoxicity by suppressing oxidative stress, mitochondrial dysfunction and cardiomyocyte apoptosis. Int J Mol Sci 2023;24:10400. doi: 10.3390/ijms241210400. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R216] 216.Luo H Jin M Hu H Ying Q Hu P Sheng W, et al. SIRT4 protects muller glial cells against apoptosis by mediating mitochondrial dynamics and oxidative stress. Mol Neurobiol 2025;62:6683-6702. doi: 10.1007/s12035-024-04349-4. [DOI] [PubMed] [Google Scholar]

[R217] 217.Chen W Zhuang A Liu C He Y Kaixin L Jiang T, et al. Mitochondrial enzyme HIBADH protects against calcium oxalate nephrolithiasis by modulating oxidative stress and apoptosis. Arch Biochem Biophys 2025;770:110452. doi: 10.1016/j.abb.2025.110452. [DOI] [PubMed] [Google Scholar]

[R218] 218.Zhang X Zhang D Li H Liu Z Yang Y Li J, et al. Melatonin-mediated suppression of mtROS-JNK-FOXO1 pathway alleviates hypoxia-induced apoptosis in porcine granulosa cells. Antioxidants (Basel) 2023;12:1881. doi: 10.3390/antiox12101881. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R219] 219.Yang Y Zhou Y Zhao X Dang R Fan P Feng F, et al. The effect of TSPO transmembrane transport-mediated paeonol mitochondrial antioxidant on dexamethasone-induced mitochondrial abnormalities, oxidative stress damage, and apoptosis in SV40-MES-13 cells. Exp Cell Res 2025;450:114674. doi: 10.1016/j.yexcr.2025.114674. [DOI] [PubMed] [Google Scholar]

[R220] 220.Peng X Wang K Zhang C Bao JP Vlf C Gao JW, et al. The mitochondrial antioxidant SS-31 attenuated lipopolysaccharide-induced apoptosis and pyroptosis of nucleus pulposus cells via scavenging mitochondrial ROS and maintaining the stability of mitochondrial dynamics. Free Radic Res 2021;55:1080-1093. doi: 10.1080/10715762.2021.2018426. [DOI] [PubMed] [Google Scholar]

[R221] 221.Yu JX, Lin M, Zhang WX, Lao FX, Huang HC. Astaxanthin prevents oxidative damage and cell apoptosis under oxidative stress involving the restoration of mitochondrial function. Cell Biochem Funct 2024;42:e70027. doi: 10.1002/cbf.70027. [DOI] [PubMed] [Google Scholar]

[R222] 222.Elmorsy EM Al Doghaither HA Al-Ghafari AB Ebrahim NA Mohamed ME Ibrahim SF, et al. Hyperoside protects human osteoblasts from phthalate-induced mitochondrial dysfunction, oxidative stress, and apoptosis. Toxicol Appl Pharmacol 2025;503:117491. doi: 10.1016/j.taap.2025.117491. [DOI] [PubMed] [Google Scholar]

[R223] 223.Yao ZK Jean YH Lin SC Lai YC Chen NF Tseng CC, et al. Manoalide induces intrinsic apoptosis by oxidative stress and mitochondrial dysfunction in human osteosarcoma cells. Antioxidants (Basel) 2023;12:1422. doi: 10.3390/antiox12071422. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R224] 224.Arun B, Gopinath P, Jha A, Tripathi N, Dastager SG, Hasan SK. Nigericin-induced apoptosis in acute myeloid leukemia via mitochondrial dysfunction and oxidative stress. Oncol Res 2025;33:2161-2174. doi: 10.32604/or.2025.062951. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R225] 225.Yan X, Wang B, Hu Y, Wang S, Zhang X. Abnormal mitochondrial quality control in neurodegenerative diseases. Front Cell Neurosci 2020;14:138. doi: 10.3389/fncel.2020.00138. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R226] 226.Liu T Sun W Guo S Yuan Z Zhu M Lu J, et al. Role of mitochondrial quality control in neurodegenerative disease progression. Front Cell Neurosci 2025;19:1588645. doi: 10.3389/fncel.2025.1588645. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R227] 227.Luo JS Zhai WH Ding LL Zhang XJ Han J Ning JQ, et al. MAMs and mitochondrial quality control: Overview and their role in Alzheimer’s disease. Neurochem Res 2024;49:2682-2698. doi: 10.1007/s11064-024-04205-w. [DOI] [PubMed] [Google Scholar]

[R228] 228.McGill Percy KC, Liu Z, Qi X. Mitochondrial dysfunction in Alzheimer’s disease: Guiding the path to targeted therapies. Neurotherapeutics 2025;22:e00525. doi: 10.1016/j.neurot.2025.e00525. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R229] 229.Tang Y, Huang Y, Wan Z, Zhou B, Wu Z. Mitochondrial quality control links two seemingly unrelated neurodegenerative diseases. Autophagy 2022;18:2495-2497. doi: 10.1080/15548627.2022.2094605. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R230] 230.Pareek G. AAA+ proteases: The first line of defense against mitochondrial damage. PeerJ 2022;10:e14350. doi: 10.7717/peerj.14350. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R231] 231.Ragupathy H, Vukku M, Barodia SK. Cell-type-specific mitochondrial quality control in the brain: A plausible mechanism of neurodegeneration. Int J Mol Sci 2023;24:14421. doi: 10.3390/ijms241914421. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R232] 232.Hu D, Liu Z, Qi X. Mitochondrial quality control strategies: Potential therapeutic targets for neurodegenerative diseases? Front Neurosci 2021;15:746873. doi: 10.3389/fnins.2021.746873. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R233] 233.Dominiak A, Gawinek E, Banaszek AA, Wilkaniec A. Mitochondrial quality control in neurodegeneration and cancer: A common denominator, distinct therapeutic challenges. Int J Mol Sci 2025;26:8693. doi: 10.3390/ijms26178693. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R234] 234.Singh D. Mitochondrial dysfunction in neurodegenerative disorders: Role of prototype targeted drug delivery solutions. Curr Drug Saf 2025. doi: 10.2174/0115748863375490250626163609. [DOI] [PubMed] [Google Scholar]

[R235] 235.Mantle D, Hargreaves IP. Mitochondrial dysfunction and neurodegenerative disorders: Role of nutritional supplementation. Int J Mol Sci 2022;23:12603. doi: 10.3390/ijms232012603. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R236] 236.Ikawa M, Okazawa H, Nakamoto Y, Yoneda M. PET imaging for oxidative stress in neurodegenerative disorders associated with mitochondrial dysfunction. Antioxidants (Basel) 2020;9:861. doi: 10.3390/antiox9090861. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R237] 237.Prasuhn J, Kunert L, Bruggemann N. Neuroimaging methods to map in vivo changes of OXPHOS and oxidative stress in neurodegenerative disorders. Int J Mol Sci 2022;23:7263. doi: 10.3390/ijms23137263. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R238] 238.Granat L, Hunt RJ, Bateman JM. Mitochondrial retrograde signalling in neurological disease. Philos Trans R Soc Lond B Biol Sci 2020;375:20190415. doi: 10.1098/rstb.2019.0415. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R239] 239.Atici AE, Crother TR, Noval Rivas M. Mitochondrial quality control in health and cardiovascular diseases. Front Cell Dev Biol 2023;11:1290046. doi: 10.3389/fcell.2023.1290046. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R240] 240.Inferrera F, Marino Y, Genovese T, Cuzzocrea S, Fusco R, Di Paola R. Mitochondrial quality control: Biochemical mechanism of cardiovascular disease. Biochim Biophys Acta Mol Cell Res 2025;1872:119906. doi: 10.1016/j.bbamcr.2025.119906. [DOI] [PubMed] [Google Scholar]

[R241] 241.Chang X Zhang W Zhao Z Ma C Zhang T Meng Q, et al. Regulation of mitochondrial quality control by natural drugs in the treatment of cardiovascular diseases: Potential and advantages. Front Cell Dev Biol 2020;8:616139. doi: 10.3389/fcell.2020.616139. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R242] 242.Oh CM, Ryu D, Cho S, Jang Y. Mitochondrial quality control in the heart: New drug targets for cardiovascular disease. Korean Circ J 2020;50:395-405. doi: 10.4070/kcj.2019.0416. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R243] 243.Zhang M Zhang T Zou R He K Huang R Feng J, et al. Mitochondrial quality control as a therapeutic target in cardiovascular disease: Mechanistic insights and future directions. J Transl Int Med 2025;13:211-240. doi: 10.1515/jtim-2025-0030. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R244] 244.Ravindran R, Gustafsson AB. Mitochondrial quality control in cardiomyocytes: Safeguarding the heart against disease and ageing. Nat Rev Cardiol 2025;22:798-813. doi: 10.1038/s41569-025-01142-1. [DOI] [PubMed] [Google Scholar]

[R245] 245.Svagusa T Sikiric S Milavic M Sepac A Seiwerth S Milicic D, et al. Heart failure in patients is associated with downregulation of mitochondrial quality control genes. Eur J Clin Invest 2023;53:e14054. doi: 10.1111/eci.14054. [DOI] [PubMed] [Google Scholar]

[R246] 246.Wang J, Zhou H. Mitochondrial quality control mechanisms as molecular targets in cardiac ischemia-reperfusion injury. Acta Pharm Sin B 2020;10:1866-1879. doi: 10.1016/j.apsb.2020.03.004. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R247] 247.Chang X, Liu R, Li R, Peng Y, Zhu P, Zhou H. Molecular mechanisms of mitochondrial quality control in ischemic cardiomyopathy. Int J Biol Sci 2023;19:426-448. doi: 10.7150/ijbs.76223. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R248] 248.Tan Y, Lei C, Tang H, Zhu X, Yi G. The hippo pathway orchestrates mitochondrial quality control: A novel focus on cardiovascular diseases. DNA Cell Biol 2020;39:1494-1505. doi: 10.1089/dna.2019.5348. [DOI] [PubMed] [Google Scholar]

[R249] 249.Ruan L, Wang Y, Zhang X, Tomaszewski A, McNamara JT, Li R. Mitochondria-associated proteostasis. Annu Rev Biophys 2020;49:41-67. doi: 10.1146/annurev-biophys-121219-081604. [DOI] [PubMed] [Google Scholar]

[R250] 250.Kanwar YS, Sun L, Xie P, Liu FY, Chen S. A glimpse of various pathogenetic mechanisms of diabetic nephropathy. Annu Rev Pathol 2011;6:395-423. doi: 10.1146/annurev.pathol.4.110807.092150. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R251] 251.Sheng J, Li X, Lei J, Gan W, Song J. Mitochondrial quality control in acute kidney disease. J Nephrol 2023;36:1283-1291. doi: 10.1007/s40620-023-01582-3. [DOI] [PubMed] [Google Scholar]

[R252] 252.Yang M Zhang Q Luo S Han Y Zhao H Jiang N, et al. DsbA-L alleviates tubular injury in diabetic nephropathy by activating mitophagy through maintenance of MAM integrity. Clin Sci (Lond) 2023;137:931-945. doi: 10.1042/CS20220787. [DOI] [PubMed] [Google Scholar]

[R253] 253.Yang M Liu Y Luo SL Liu CB Jiang N Li CR, et al. DsbA-L ameliorates renal aging and renal fibrosis by maintaining mitochondrial homeostasis. Acta Pharmacol Sin 2024;45:777-789. doi: 10.1038/s41401-023-01216-1. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R254] 254.Gao P, Yang M, Chen X, Xiong S, Liu J, Sun L. DsbA-L deficiency exacerbates mitochondrial dysfunction of tubular cells in diabetic kidney disease. Clin Sci (Lond) 2020;134:677-694. doi: 10.1042/CS20200005. [DOI] [PubMed] [Google Scholar]

[R255] 255.Bhatia D, Capili A, Choi ME. Mitochondrial dysfunction in kidney injury, inflammation, and disease: Potential therapeutic approaches. Kidney Res Clin Pract 2020;39:244-258. doi: 10.23876/j.krcp.20.082. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R256] 256.Tan ZX, Zhu WZ. Regulatory mechanisms of mitochondrial dynamics and its emerging role in renal pathophysiology (in Chinese). Acta Physiologica Sinica 2024;76:148-160. [PubMed] [Google Scholar]

[R257] 257.Zhan M, Brooks C, Liu F, Sun L, Dong Z. Mitochondrial dynamics: Regulatory mechanisms and emerging role in renal pathophysiology. Kidney Int 2013;83:568-581. doi: 10.1038/ki.2012.441. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R258] 258.Yang S Han Y Liu J Song P Xu X Zhao L, et al. Mitochondria: A novel therapeutic target in diabetic nephropathy. Curr Med Chem 2017;24:3185-3202. doi: 10.2174/0929867324666170509121003. [DOI] [PubMed] [Google Scholar]

[R259] 259.Yang M Liu C Jiang N Liu Y Luo S Li C, et al. Mitochondrial homeostasis: A potential target for delaying renal aging. Front Pharmacol 2023;14:1191517. doi: 10.3389/fphar.2023.1191517. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R260] 260.Bhatia D, Choi ME. The emerging role of mitophagy in kidney diseases. J Life Sci (Westlake Village) 2019;1:13-22. doi: 10.36069/jols/20191203. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R261] 261.Fan X, Wu L, Wang F, Liu D, Cen X, Xia H. Mitophagy regulates kidney diseases. Kidney Dis (Basel) 2024;10:573-587. doi: 10.1159/000541486. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R262] 262.Wang Y, Cai J, Tang C, Dong Z. Mitophagy in acute kidney injury and kidney repair. Cells 2020;9:338. doi: 10.3390/cells9020338. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R263] 263.Sabry MM Ahmed MM Maksoud OMA Rashed L Morcos MA El-Maaty AA, et al. Carnitine, apelin and resveratrol regulate mitochondrial quality control (QC) related proteins and ameliorate acute kidney injury: Role of hydrogen peroxide. Arch Physiol Biochem 2022;128:1391-1400. doi: 10.1080/13813455.2020.1773504. [DOI] [PubMed] [Google Scholar]

[R264] 264.Hurtado K, Scholpa NE, Schnellmann JG, Schnellmann RG. Serotonin regulation of mitochondria in kidney diseases. Pharmacol Res 2024;203:107154. doi: 10.1016/j.phrs.2024.107154. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R265] 265.Srivastava A, Tomar B, Sharma D, Rath SK. Mitochondrial dysfunction and oxidative stress: Role in chronic kidney disease. Life Sci 2023;319:121432. doi: 10.1016/j.lfs.2023.121432. [DOI] [PubMed] [Google Scholar]

[R266] 266.Sang XY Xiao JJ Liu Q Zhu R Dai JJ Zhang C, et al. Regulators of calcineurin 1 deficiency attenuates tubulointerstitial fibrosis through improving mitochondrial fitness. FASEB J 2020;34. doi: 10.1096/fj.202000781RRR. [DOI] [PubMed] [Google Scholar]

[R267] 267.Yang X Feng J Liang W Zhu Z Chen Z Hu J, et al. Roles of SIRT6 in kidney disease: A novel therapeutic target. Cell Mol Life Sci 2021;79:53. doi: 10.1007/s00018-021-04061-9. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R268] 268.Xu L Wang J Yu H Mei H He P Wang M, et al. GLIS1 alleviates cell senescence and renal fibrosis through PGC1-alpha mediated mitochondrial quality control in kidney aging. Free Radic Biol Med 2023;209:171-184. doi: 10.1016/j.freeradbiomed.2023.09.037. [DOI] [PubMed] [Google Scholar]

[R269] 269.Zhang M Tong Z Wang Y Fu W Meng Y Huang J, et al. Relationship between ferroptosis and mitophagy in renal fibrosis: A systematic review. J Drug Target 2023;31:858-866. doi: 10.1080/1061186X.2023.2250574. [DOI] [PubMed] [Google Scholar]

[R270] 270.Xiao L Xu X Zhang F Wang M Xu Y Tang D, et al. The mitochondria-targeted antioxidant MitoQ ameliorated tubular injury mediated by mitophagy in diabetic kidney disease via Nrf2/PINK1. Redox Biol 2017;11:297-311. doi: 10.1016/j.redox.2016.12.022. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R271] 271.Liu S, Yuan Y, Xue Y, Xing C, Zhang B. Podocyte injury in diabetic kidney disease: A focus on mitochondrial dysfunction. Front Cell Dev Biol 2022;10:832887. doi: 10.3389/fcell.2022.832887. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R272] 272.Dai W, Lu H, Chen Y, Yang D, Sun L, He L. The loss of mitochondrial quality control in diabetic kidney disease. Front Cell Dev Biol 2021;9:706832. doi: 10.3389/fcell.2021.706832. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R273] 273.Bhatia D, Choi ME. Autophagy and mitophagy: Physiological implications in kidney inflammation and diseases. Am J Physiol Renal Physiol 2023;325:F1-F21. doi: 10.1152/ajprenal.00012.2023. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R274] 274.Han Y Xu X Tang C Gao P Chen X Xiong X, et al. Reactive oxygen species promote tubular injury in diabetic nephropathy: The role of the mitochondrial ros-txnip-nlrp3 biological axis. Redox Biol 2018;16:32-46. doi: 10.1016/j.redox.2018.02.013. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R275] 275.Sun L Xiao L Nie J Liu FY Ling GH Zhu XJ, et al. p66Shc mediates high-glucose and angiotensin II-induced oxidative stress renal tubular injury via mitochondrial-dependent apoptotic pathway. Am J Physiol Renal Physiol 2010;299:F1014-F1025. doi: 10.1152/ajprenal.00414.2010. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R276] 276.Prem PN, Swaminathan H, Kurian GA. The temporal relationship between mitochondrial quality and renal tissue recovery following ischemia-reperfusion injury. Heliyon 2025;11:e41634. doi: 10.1016/j.heliyon.2025.e41634. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R277] 277.Zanini G Micheloni G Sinigaglia G Selleri V Mattioli AV Nasi M, et al. Modulation of Lonp1 activity by small compounds. Biomolecules 2025;15:553. doi: 10.3390/biom15040553. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R278] 278.Liu Y Zhang L Zhang S Liu J Li X Yang K, et al. ATF5 regulates tubulointerstitial injury in diabetic kidney disease via mitochondrial unfolded protein response. Mol Med 2023;29:57. doi: 10.1186/s10020-023-00651-4. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R279] 279.Yu Y Chen M Guo Q Shen L Liu X Pan J, et al. Human umbilical cord mesenchymal stem cell exosome-derived miR-874-3p targeting RIPK1/PGAM5 attenuates kidney tubular epithelial cell damage. Cell Mol Biol Lett 2023;28:12. doi: 10.1186/s11658-023-00425-0. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R280] 280.Lee TW, Bae E, Kim JH, Jung MH, Park DJ. Zileuton attenuates acute kidney injury in glycerol-induced rhabdomyolysis by regulating myeloid-derived suppressor cells in mice. Int J Mol Sci 2025;26:8353. doi: 10.3390/ijms26178353. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R281] 281.Luo S Yang M Zhao H Han Y Liu Y Xiong X, et al. Mitochondrial DNA-dependent inflammation in kidney diseases. Int Immunopharmacol 2022;107:108637. doi: 10.1016/j.intimp.2022.108637. [DOI] [PubMed] [Google Scholar]

[R282] 282.Zhang L Xu Z Jing J Chai G Xie G Ru Y, et al. Age-dependent accumulation of mitochondrial tRNA mutations in mouse kidneys linked to mitochondrial kidney diseases. Nat Aging 2025;5:1317-1339. doi: 10.1038/s43587-025-00909-y. [DOI] [PubMed] [Google Scholar]

[R283] 283.Duan T Sun L Xi Y Li C Zhao Q Xu L, et al. Mito-tempo ameliorates tubular injury of diabetic nephropathy via inhibiting mt-dsRNA release and PKR/eIF2alpha pathway activation. Free Radic Biol Med 2025;237:147-159. doi: 10.1016/j.freeradbiomed.2025.05.431. [DOI] [PubMed] [Google Scholar]

[R284] 284.Duan T Sun L Ding K Zhao Q Xu L Liu C, et al. Mitochondrial RNA metabolism, a potential therapeutic target for mitochondria-related diseases. Chin Med J 2025;138:808-818. doi: 10.1097/CM9.0000000000003516. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R285] 285.Tang C, Cai J, Yin XM, Weinberg JM, Venkatachalam MA, Dong Z. Mitochondrial quality control in kidney injury and repair. Nat Rev Nephrol 2021;17:299-318. doi: 10.1038/s41581-020-00369-0. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R286] 286.Ito M, Gurumani MZ, Merscher S, Fornoni A. Glucose- and non-glucose-induced mitochondrial dysfunction in diabetic kidney disease. Biomolecules 2022;12:351. doi: 10.3390/biom12030351. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R287] 287.Shin S, Kim J, Lee JY, Kim J, Oh CM. Mitochondrial quality control: Its role in metabolic dysfunction-associated steatotic liver disease (MASLD). J Obes Metab Syndr 2023;32:289-302. doi: 10.7570/jomes23054. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R288] 288.Cioffi F Giacco A Petito G de Matteis R Senese R Lombardi A, et al. Altered mitochondrial quality control in rats with metabolic dysfunction-associated fatty liver disease (MAFLD) induced by high-fat feeding. Genes (Basel) 2022;13:315. doi: 10.3390/genes13020315. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R289] 289.Giacco A Petito G Silvestri E Scopigno N Vigliotti M Mercurio G, et al. Comparative effects of 3,5-diiodo-L-thyronine and 3,5,3′-triiodo-L-thyronine on mitochondrial damage and cGAS/STING-driven inflammation in liver of hypothyroid rats. Front Endocrinol (Lausanne) 2024;15:1432819. doi: 10.3389/fendo.2024.1432819. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R290] 290.Cai C Wu F He J Zhang Y Shi N Peng X, et al. Mitochondrial quality control in diabetic cardiomyopathy: From molecular mechanisms to therapeutic strategies. Int J Biol Sci 2022;18:5276-5290. doi: 10.7150/ijbs.75402. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R291] 291.Zhou Y Suo W Zhang X Liang J Zhao W Wang Y, et al. Targeting mitochondrial quality control for diabetic cardiomyopathy: Therapeutic potential of hypoglycemic drugs. Biomed Pharmacother 2023;168:115669. doi: 10.1016/j.biopha.2023.115669. [DOI] [PubMed] [Google Scholar]

[R292] 292.Li Q, Shang J, Inagi R. Control of mitochondrial quality: A promising target for diabetic kidney disease treatment. Kidney Int Rep 2025;10:994-1010. doi: 10.1016/j.ekir.2024.12.029. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R293] 293.Liu P, Chen Y, Xiao J, Zhu W, Yan X, Chen M. Protective effect of natural products in the metabolic-associated kidney diseases via regulating mitochondrial dysfunction. Front Pharmacol 2022;13:1093397. doi: 10.3389/fphar.2022.1093397. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R294] 294.Prasun P. Mitochondrial dysfunction in metabolic syndrome. Biochim Biophys Acta Mol Basis Dis 2020;1866:165838. doi: 10.1016/j.bbadis.2020.165838. [DOI] [PubMed] [Google Scholar]

[R295] 295.Todosenko N Khaziakhmatova O Malashchenko V Yurova K Bograya M Beletskaya M, et al. Mitochondrial dysfunction associated with mtDNA in metabolic syndrome and obesity. Int J Mol Sci 2023;24:12012. doi: 10.3390/ijms241512012. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R296] 296.Zhang Q Ren J Wang F Pan M Cui L Li M, et al. Mitochondrial and glucose metabolic dysfunctions in granulosa cells induce impaired oocytes of polycystic ovary syndrome through Sirtuin 3. Free Radic Biol Med 2022;187:1-16. doi: 10.1016/j.freeradbiomed.2022.05.010. [DOI] [PubMed] [Google Scholar]

[R297] 297.Zeng X, Huang Q, Long SL, Zhong Q, Mo Z. Mitochondrial dysfunction in polycystic ovary syndrome. DNA Cell Biol 2020;39:1401-1409. doi: 10.1089/dna.2019.5172. [DOI] [PubMed] [Google Scholar]

[R298] 298.Moisoi N. Mitochondrial proteases modulate mitochondrial stress signalling and cellular homeostasis in health and disease. Biochimie 2024;226:165-179. doi: 10.1016/j.biochi.2024.06.005. [DOI] [PubMed] [Google Scholar]

[R299] 299.Karbowski M, Oshima Y, Verhoeven N. Mitochondrial proteotoxicity: Implications and ubiquitin-dependent quality control mechanisms. Cell Mol Life Sci 2022;79:574. doi: 10.1007/s00018-022-04604-8. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R300] 300.Zhou S Xiong X Hou J Duan Q Zheng Y Jiang T, et al. NAD+-boosters improve mitochondria quality control in Parkinson’s disease models via mitochondrial UPR. Adv Sci (Weinh) 2025;12:e08503. doi: 10.1002/advs.202408503. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R301] 301.Fallahi F Mostafavinia A Sharifi Z Mohaghegh Shalmani L Amini A Ahmadi H, et al. Effects of photobiomodulation on mitochondrial function in diabetic adipose-derived stem cells in vitro. Spectrochim Acta A Mol Biomol Spectrosc 2023;285:121835. doi: 10.1016/j.saa.2022.121835. [DOI] [PubMed] [Google Scholar]

[R302] 302.Chen Q, Zhang Q, Amrouche AT, Huang W, Lu B. Asperuloside, the bioactive compound in the edible Eucommia ulmoides male flower, delays muscle aging by daf-16 mediated improvement in mitochondrial dysfunction. Food Funct 2023;14:5562-5575. doi: 10.1039/d3fo01024d. [DOI] [PubMed] [Google Scholar]

[R303] 303.Yeon MH, Seo E, Lee JH, Jun HS. Bavachin and corylifol a improve muscle atrophy by enhancing mitochondria quality control in type 2 diabetic mice. Antioxidants (Basel) 2023;12:137. doi: 10.3390/antiox12010137. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R304] 304.Inigo JR, Chandra D. The mitochondrial unfolded protein response (UPR(mt)): Shielding against toxicity to mitochondria in cancer. J Hematol Oncol 2022;15:98. doi: 10.1186/s13045-022-01317-0. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R305] 305.Liu Y Wang H Zhang S Peng N Hai S Zhao H, et al. The role of mitochondrial biogenesis, mitochondrial dynamics and mitophagy in gastrointestinal tumors. Cancer Cell Int 2025;25:46. doi: 10.1186/s12935-025-03685-2. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R306] 306.Han P, Ren X, Qu X, Meng Y. The regulatory mechanisms of dynamin-related protein 1 in tumor development and therapy. Cancer Biother Radiopharm 2021;36:10-17. doi: 10.1089/cbr.2020.3791. [DOI] [PubMed] [Google Scholar]

[R307] 307.Gallo Cantafio ME, Torcasio R, Viglietto G, Amodio N. Non-coding RNA-dependent regulation of mitochondrial dynamics in cancer pathophysiology. Noncoding RNA 2023;9:16. doi: 10.3390/ncrna9010016. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R308] 308.Sano H Futamura M Gaowa S Kamino H Nakamura Y Yamaguchi K, et al. p53/Mieap-regulated mitochondrial quality control plays an important role as a tumor suppressor in gastric and esophageal cancers. Biochem Biophys Res Commun 2020;529:582-589. doi: 10.1016/j.bbrc.2020.05.168. [DOI] [PubMed] [Google Scholar]

[R309] 309.Nouri K, Feng Y, Schimmer AD. Mitochondrial ClpP serine protease-biological function and emerging target for cancer therapy. Cell Death Dis 2020;11:841. doi: 10.1038/s41419-020-03062-z. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R310] 310.Gagliardi S Mitruccio M Di Corato R Romano R Aloisi A Rinaldi R, et al. Defects of mitochondria-lysosomes communication induce secretion of mitochondria-derived vesicles and drive chemoresistance in ovarian cancer cells. Cell Commun Signal 2024;22:165. doi: 10.1186/s12964-024-01507-y. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R311] 311.Peng X Gao Y Liu J Shi X Li W Ma Y, et al. Mitochondria-derived vesicles: A promising and potential target for tumour therapy. Clin Transl Med 2025;15:e70320. doi: 10.1002/ctm2.70320. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R312] 312.Wang Q Chai D Sobhani N Sun N Neeli P Zheng J, et al. C1QBP regulates mitochondrial plasticity to impact tumor progression and antitumor immune response. Front Physiol 2022;13:1012112. doi: 10.3389/fphys.2022.1012112. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R313] 313.Deng X Wang Q Cheng M Chen Y Yan X Guo R, et al. Pyruvate dehydrogenase kinase 1 interferes with glucose metabolism reprogramming and mitochondrial quality control to aggravate stress damage in cancer. J Cancer 2020;11:962-973. doi: 10.7150/jca.34330. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R314] 314.Sandoval-Acuna C Torrealba N Tomkova V Jadhav SB Blazkova K Merta L, et al. Targeting mitochondrial iron metabolism suppresses tumor growth and metastasis by inducing mitochondrial dysfunction and mitophagy. Cancer Res 2021;81:2289-2303. doi: 10.1158/0008-5472.CAN-20-1628. [DOI] [PubMed] [Google Scholar]

[R315] 315.Ma Z, Han H, Zhao Y. Mitochondrial dysfunction-targeted nanosystems for precise tumor therapeutics. Biomaterials 2023;293:121947. doi: 10.1016/j.biomaterials.2022.121947. [DOI] [PubMed] [Google Scholar]

[R316] 316.Xia Y, Gao B, Zhang X. Targeting mitochondrial quality control of T cells: Regulating the immune response in HCC. Front Oncol 2022;12:993437. doi: 10.3389/fonc.2022.993437. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R317] 317.Greier MDC Runge A Dudas J Hartl R Santer M Dejaco D, et al. Cytotoxic response of tumor-infiltrating lymphocytes of head and neck cancer slice cultures under mitochondrial dysfunction. Front Oncol 2024;14:1364577. doi: 10.3389/fonc.2024.1364577. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R318] 318.Pei W Dai L Li M Cao S Xiao Y Yang Y, et al. Targeting mitochondrial quality control for the treatment of triple-negative breast cancer: From molecular mechanisms to precision therapy. Biomolecules 2025;15:970. doi: 10.3390/biom15070970. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R319] 319.Fang X, Wu H, Wei J, Miao R, Zhang Y, Tian J. Research progress on the pharmacological effects of berberine targeting mitochondria. Front Endocrinol (Lausanne) 2022;13:982145. doi: 10.3389/fendo.2022.982145. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R320] 320.Gupta N, Curcic M, Srivastava SK. Proguanil suppresses breast tumor growth in vitro and in vivo by inducing apoptosis via mitochondrial dysfunction. Cancers (Basel) 2024;16:872. doi: 10.3390/cancers16050872. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R321] 321.Shi C Huang H Zhou X Zhang Z Ma H Yao Q, et al. Reversing multidrug resistance by inducing mitochondrial dysfunction for enhanced chemo-photodynamic therapy in tumor. ACS Appl Mater Interfaces 2021;13:45259-45268. doi: 10.1021/acsami.1c12725. [DOI] [PubMed] [Google Scholar]

[R322] 322.Wei T Chen L Shi P Wang C Peng Y Yang J, et al. Platinum (IV) drugs with cannabidiol inducing mitochondrial dysfunction and synergistically enhancing anti-tumor effects. J Inorg Biochem 2024;254:112515. doi: 10.1016/j.jinorgbio.2024.112515. [DOI] [PubMed] [Google Scholar]

[R323] 323.Marzetti E Coelho-Junior HJ Calvani R Girolimetti G Di Corato R Ciciarello F, et al. Mitochondria-derived vesicles and inflammatory profiles of adults with long COVID supplemented with red beetroot juice: Secondary analysis of a randomized controlled trial. Int J Mol Sci 2025;26:1224. doi: 10.3390/ijms26031224. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R324] 324.Xu W Dong L Dai J Zhong L Ouyang X Li J, et al. The interconnective role of the UPS and autophagy in the quality control of cancer mitochondria. Cell Mol Life Sci 2025;82:42. doi: 10.1007/s00018-024-05556-x. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R325] 325.Pickrell AM, Youle RJ. The roles of PINK1, parkin, and mitochondrial fidelity in Parkinson’s disease. Neuron 2015;85:257-273. doi: 10.1016/j.neuron.2014.12.007. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R326] 326.Joshi AU, Saw NL, Vogel H, Cunnigham AD, Shamloo M, Mochly-Rosen D. Inhibition of Drp1/Fis1 interaction slows progression of amyotrophic lateral sclerosis. EMBO Mol Med 2018;10:e8166. doi: 10.15252/emmm.201708166. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R327] 327.Qiao C, Hu XQ, Xu SH, Yao MF, Liu JP, Cao L. Targeting NME3 to restore mitochondrial fission-fusion balance defines a novel disease-modifying strategy for Parkinson’s disease. CNS Neurosci Ther 2026;32:e70822. doi: 10.1002/cns.70822. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R328] 328.Ma J Yang Y Zang C Chen Q Jiang Y Dong Y, et al. Inhibiting mitochondrial excessive fission alleviates the neuronal damage in Parkinson’s disease via regulating PGC-1alpha mediated mitochondrial biogenesis. Exp Neurol 2025;391:115288. doi: 10.1016/j.expneurol.2025.115288. [DOI] [PubMed] [Google Scholar]

[R329] 329.Chang P Xu M Zhu J Bian J Lu Y Luo Q, et al. Pharmacological inhibition of mitochondrial division attenuates simulated high-altitude exposure-induced memory impairment in mice: Involvement of inhibition of microglia-mediated synapse elimination. CNS Neurosci Ther 2025;31:e70473. doi: 10.1111/cns.70473. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R330] 330.Arbo BD Andre-Miral C Nasre-Nasser RG Schimith LE Santos MG Costa-Silva D, et al. Resveratrol derivatives as potential treatments for Alzheimer’s and Parkinson’s disease. Front Aging Neurosci 2020;12:103. doi: 10.3389/fnagi.2020.00103. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R331] 331.Saadh MJ Nazar Saeed T Fawzi Al-Hussainy A Kyada A Ballal S Kundlas M, et al. Mechanistic insights into ubiquinone Q10 in Parkinson’s disease: Mitochondrial protection, ferroptosis inhibition, and antioxidant recycling. Arch Physiol Biochem 2026;132:134-150. doi: 10.1080/13813455.2025.2541698. [DOI] [PubMed] [Google Scholar]

[R332] 332.Zhang Y Liu T Li X Liu S Zhu X Ren Y, et al. Neuroprotective effects of idebenone in a zebrafish model of Parkinson’s disease via regulating autophagy, mitigating apoptosis and oxidative stress. Neuroscience 2026;599:52-64. doi: 10.1016/j.neuroscience.2026.02.016. [DOI] [PubMed] [Google Scholar]

[R333] 333.Zhang Q, Zhang W, Yuan X, Peng X, Hu G. Urolithin A in central nervous system disorders: Therapeutic applications and challenges. Biomedicines 2025;13:1553. doi: 10.3390/biomedicines13071553. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R334] 334.Maitra S, Ham DW, Baek M, Choe YJ, Kim NC. FDA-approved PDE4 inhibitors alleviate the dominant toxicity of ALS-FTD-associated CHCHD10(S59L) in Drosophila and human cells. iScience 2026;29:114879. doi: 10.1016/j.isci.2026.114879. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R335] 335.Nesci S, Rubattu S. Mitochondrial permeability transition pore: The cardiovascular disease’s molecular Achilles heel. Biomedicines 2025;13:3014. doi: 10.3390/biomedicines13123014. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R336] 336.Lees JG Greening DW Rudd DA Cross J Rosdah AA Lai X, et al. Cardiac-targeted delivery of a novel Drp1 inhibitor for acute cardioprotection. J Mol Cell Cardiol Plus 2024;9:100085. doi: 10.1016/j.jmccpl.2024.100085. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R337] 337.Zhang W, Siraj S, Zhang R, Chen Q. Mitophagy receptor FUNDC1 regulates mitochondrial homeostasis and protects the heart from I/R injury. Autophagy 2017;13:1080-1081. doi: 10.1080/15548627.2017.1300224. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R338] 338.Fordjour PA Wang L Gao H Li L Wang Y Nyagblordzro M, et al. Targeting BNIP3 in inflammation-mediated heart failure: A novel concept in heart failure therapy. Heart Fail Rev 2016;21:489-497. doi: 10.1007/s10741-016-9557-4. [DOI] [PubMed] [Google Scholar]

[R339] 339.Halestrap AP, Pasdois P. The role of the mitochondrial permeability transition pore in heart disease. Biochim Biophys Acta 2009;1787:1402-1415. doi: 10.1016/j.bbabio.2008.12.017. [DOI] [PubMed] [Google Scholar]

[R340] 340.van Rinsum A, Hu L, Qi X, Keijer J, Zhang D. Mitochondria-targeted antioxidants prevent tachypacing-induced contractile dysfunction in in vitro cardiomyocyte and in vivo drosophila models of atrial fibrillation. Antioxidants (Basel) 2025;14:1444. doi: 10.3390/antiox14121444. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R341] 341.Li T Guo C Liu Q Jing F Zhao M Xiong H, et al. Mesenchymal stem cells inhibit mitochondrial fission by upregulating armadillo repeat containing 1, ameliorating oxidative stress in renal fibrosis. Stem Cell Res Ther 2025;16:584. doi: 10.1186/s13287-025-04706-7. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R342] 342.Ma T Yu Y Luo H Zhang Z Wei M Tian C, et al. CircAASS alleviates renal injury and fibrosis by regulating mitochondrial homeostasis in tubular epithelial cells. Autophagy 2026;22:182-206. doi: 10.1080/15548627.2025.2581212. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R343] 343.Birk AV Liu S Soong Y Mills W Singh P Warren JD, et al. The mitochondrial-targeted compound SS-31 re-energizes ischemic mitochondria by interacting with cardiolipin. J Am Soc Nephrol 2013;24:1250-1261. doi: 10.1681/ASN.2012121216. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R344] 344.Li L, Hu F. Mitophagy in tumor: Foe or friend? Endokrynol Pol 2023;74:511-519. doi: 10.5603/ep.95652. [DOI] [PubMed] [Google Scholar]

[R345] 345.Alam M, Ali S, Mohammad T, Hasan GM, Yadav DK, Hassan MI. B Cell lymphoma 2: A potential therapeutic target for cancer therapy. Int J Mol Sci 2021;22:10442. doi: 10.3390/ijms221910442. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R346] 346.Molina JR Sun Y Protopopova M Gera S Bandi M Bristow C, et al. An inhibitor of oxidative phosphorylation exploits cancer vulnerability. Nat Med 2018;24:1036-1046. doi: 10.1038/s41591-018-0052-4. [DOI] [PubMed] [Google Scholar]

[R347] 347.Low LE Kong CK Yap WH Siva SP Gan SH Siew WS, et al. Hydroxychloroquine: Key therapeutic advances and emerging nanotechnological landscape for cancer mitigation. Chem Biol Interact 2023;386:110750. doi: 10.1016/j.cbi.2023.110750. [DOI] [PubMed] [Google Scholar]

[R348] 348.Davids MS, Letai A. ABT-199: Taking dead aim at BCL-2. Cancer Cell 2013;23:139-141. doi: 10.1016/j.ccr.2013.01.018. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R349] 349.Mehmood T, Nasir Q, Younis I, Muanprasat C. Inhibition of mitochondrial dynamics by mitochondrial division inhibitor-1 suppresses cell migration and metastatic markers in colorectal cancer HCT116 cells. J Exp Pharmacol 2025;17:143-157. doi: 10.2147/JEP.S510578. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R350] 350.Khetarpal SA Li H Vitale T Rhee J Challa S Castro C, et al. Cardiac adaptation to endurance exercise training requires suppression of GDF15 via PGC-1alpha. Nat Cardiovasc Res 2025;4:1277-1294. doi: 10.1038/s44161-025-00712-3. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R351] 351.Hardie DG. Sensing of energy and nutrients by AMP-activated protein kinase. Am J Clin Nutr 2011;93:891S-896S. doi: 10.3945/ajcn.110.001925. [DOI] [PubMed] [Google Scholar]

[R352] 352.Su Z Guo Y Huang X Feng B Tang L Zheng G, et al. Phytochemicals: Targeting mitophagy to treat metabolic disorders. Front Cell Dev Biol 2021;9:686820. doi: 10.3389/fcell.2021.686820. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R353] 353.Di Francesco A Deighan AG Litichevskiy L Chen Z Luciano A Robinson L, et al. Dietary restriction impacts health and lifespan of genetically diverse mice. Nature 2024;634:684-692. doi: 10.1038/s41586-024-08026-3. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R354] 354.Tulipano G. Integrated or independent actions of metformin in target tissues underlying its current use and new possible applications in the endocrine and metabolic disorder area. Int J Mol Sci 2021;22:13068. doi: 10.3390/ijms222313068. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R355] 355.Gao Y Wei X Wei P Lu H Zhong L Tan J, et al. MOTS-c functionally prevents metabolic disorders. Metabolites 2023;13:125. doi: 10.3390/metabo13010125. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R356] 356.Liu C Sun M Zhao Z Yang Y Yang Y Zhao Y, et al. Urolithin A: A multi-target therapeutic candidate derived from the gut microbiota for obesity and metabolic dysfunction. Front Endocrinol (Lausanne) 2026;17:1786776. doi: 10.3389/fendo.2026.1786776. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R357] 357.Li QC, Wang SQ, Cao ZZ, Zhou SH. Enhanced mitophagy in cholesteatoma epithelial cells. Otol Neurotol 2023;44:688-694. doi: 10.1097/MAO.0000000000003986. [DOI] [PubMed] [Google Scholar]

[R358] 358.Pradeepkiran JA, Hindle A, Kshirsagar S, Reddy PH. Are mitophagy enhancers therapeutic targets for Alzheimer’s disease? Biomed Pharmacother 2022;149:112918. doi: 10.1016/j.biopha.2022.112918. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R359] 359.Dorn GW,, 2nd. Small molecules that enhance mitophagy to delay aging and neurodegeneration. J Cardiovasc Aging 2022;2:45. doi: 10.20517/jca.2022.36. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R360] 360.Hu S Zhang C Ni L Huang C Chen D Shi K, et al. Stabilization of HIF-1alpha alleviates osteoarthritis via enhancing mitophagy. Cell Death Dis 2020;11:481. doi: 10.1038/s41419-020-2680-0. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R361] 361.Ramakrishnan RK Bajbouj K Hachim MY Mogas AK Mahboub B Olivenstein R, et al. Enhanced mitophagy in bronchial fibroblasts from severe asthmatic patients. PLoS One 2020;15:e0242695. doi: 10.1371/journal.pone.0242695. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R362] 362.Yang C, Xiao C, Ding Z, Zhai X, Liu J, Yu M. Canagliflozin mitigates diabetic cardiomyopathy through enhanced PINK1-parkin mitophagy. Int J Mol Sci 2024;25:7008. doi: 10.3390/ijms25137008. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R363] 363.Zheng C, Nguyen KK, Vishnivetskiy SA, Gurevich VV, Gurevich EV. Arrestin-3 binds parkin and enhances parkin-dependent mitophagy. J Neurochem 2025;169:e16043. doi: 10.1111/jnc.16043. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R364] 364.Kook S, Zhan X, Thibeault K, Ahmed MR, Gurevich VV, Gurevich EV. Mdm2 enhances ligase activity of parkin and facilitates mitophagy. Sci Rep 2020;10:5028. doi: 10.1038/s41598-020-61796-4. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R365] 365.Varghese N, Werner S, Grimm A, Eckert A. Dietary mitophagy enhancer: A strategy for healthy brain aging? Antioxidants (Basel) 2020;9:932. doi: 10.3390/antiox9100932. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R366] 366.Zhang SQ Niu Z Anisimov A Shi F Deng S Xiao X, et al. NR1D1 Inhibition enhances autophagy and mitophagy in Alzheimer’s disease models. Aging Dis 2025. doi: 10.14336/AD.2024.1654. [DOI] [PubMed] [Google Scholar]

[R367] 367.Gao LP Xiao K Wu YZ Chen DD Yang XH Shi Q, et al. Enhanced mitophagy activity in prion-infected cultured cells and prion-infected experimental mice via a Pink1/Parkin-dependent mitophagy pathway. ACS Chem Neurosci 2020;11:814-829. doi: 10.1021/acschemneuro.0c00039. [DOI] [PubMed] [Google Scholar]

[R368] 368.Luo P An Y He J Xing X Zhang Q Liu X, et al. Icaritin with autophagy/mitophagy inhibitors synergistically enhances anticancer efficacy and apoptotic effects through PINK1/Parkin-mediated mitophagy in hepatocellular carcinoma. Cancer Lett 2024;587:216621. doi: 10.1016/j.canlet.2024.216621. [DOI] [PubMed] [Google Scholar]

[R369] 369.Han D Su T Wang M Zhang R Xu H Chu R, et al. JAK2 inhibitor protects the septic heart through enhancing mitophagy in cardiomyocytes. Biomed Pharmacother 2024;178:117279. doi: 10.1016/j.biopha.2024.117279. [DOI] [PubMed] [Google Scholar]

[R370] 370.Liu C Peng Z Li P Fu H Feng J Zhang Y, et al. LncRNA RMST suppressed GBM cell mitophagy through enhancing FUS SUMOylation. Mol Ther Nucleic Acids 2020;19:1198-1208. doi: 10.1016/j.omtn.2020.01.008. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R371] 371.Zhang P, Chen S, Tang H, Fang W, Chen K, Chen X. CoQ10 protects against acetaminophen-induced liver injury by enhancing mitophagy. Toxicol Appl Pharmacol 2021;410:115355. doi: 10.1016/j.taap.2020.115355. [DOI] [PubMed] [Google Scholar]

[R372] 372.Li SJ Tetri LH Vijayan V Elezaby A Chiang CH Lopez I, et al. Excessive mitochondrial fission and associated extracellular mitochondria mediate cardiac dysfunction in obesity cardiomyopathy. Life Sci 2025;373:123658. doi: 10.1016/j.lfs.2025.123658. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R373] 373.Zhou L, Su W, Wang Y, Zhang Y, Xia Z, Lei S. FOXO1 reduces STAT3 activation and causes impaired mitochondrial quality control in diabetic cardiomyopathy. Diabetes Obes Metab 2024;26:732-744. doi: 10.1111/dom.15369. [DOI] [PubMed] [Google Scholar]

[R374] 374.Chang X Zhou S Liu J Wang Y Guan X Wu Q, et al. Zishen Tongyang Huoxue decoction (TYHX) alleviates sinoatrial node cell ischemia/reperfusion injury by directing mitochondrial quality control via the VDAC1-beta-tubulin signaling axis. J Ethnopharmacol 2024;320:117371. doi: 10.1016/j.jep.2023.117371. [DOI] [PubMed] [Google Scholar]

[R375] 375.Shandilya C, Mani S. Rho kinase isoforms in neurodegeneration: From cellular functions to therapeutic targets. Mol Biol Rep 2025;52:846. doi: 10.1007/s11033-025-10947-9. [DOI] [PubMed] [Google Scholar]

[R376] 376.Shi W, Tan C, Liu C, Chen D. Mitochondrial fission mediated by Drp1-Fis1 pathway and neurodegenerative diseases. Rev Neurosci 2023;34:275-294. doi: 10.1515/revneuro-2022-0056. [DOI] [PubMed] [Google Scholar]

[R377] 377.Wang J Zhuang H Jia L He X Zheng S Ji K, et al. Nuclear receptor subfamily 4 group A member 1 promotes myocardial ischemia/reperfusion injury through inducing mitochondrial fission factor-mediated mitochondrial fragmentation and inhibiting FUN14 domain containing 1-depedent mitophagy. Int J Biol Sci 2024;20:4458-4475. doi: 10.7150/ijbs.95853. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R378] 378.Zhang R Xue MY Liu BS Wang WJ Fan XH Zheng BY, et al. Aldehyde dehydrogenase 2 preserves mitochondrial morphology and attenuates hypoxia/reoxygenation-induced cardiomyocyte injury. World J Emerg Med 2020;11:246-254. doi: 10.5847/wjem.j.1920-8642.2020.04.007. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R379] 379.Ying J Deng X Du R Ding Q Tian H Lin Y, et al. Mitochondrial modulation treating postoperative cognitive dysfunction neuroprotection via DRP1 inhibition by Mdivi1. Sci Rep 2024;14:26155. doi: 10.1038/s41598-024-75548-1. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R380] 380.Yao S Pang M Wang Y Wang X Lin Y Lv Y, et al. Mesenchymal stem cell attenuates spinal cord injury by inhibiting mitochondrial quality control-associated neuronal ferroptosis. Redox Biol 2023;67:102871. doi: 10.1016/j.redox.2023.102871. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R381] 381.Qin YR Ma CQ Jiang JH Wang DP Zhang QQ Liu MR, et al. Artesunate restores mitochondrial fusion-fission dynamics and alleviates neuronal injury in Alzheimer’s disease models. J Neurochem 2022;162:290-304. doi: 10.1111/jnc.15620. [DOI] [PubMed] [Google Scholar]

[R382] 382.Qiu K Zou W Fang H Hao M Mehta K Tian Z, et al. Light-activated mitochondrial fission through optogenetic control of mitochondria-lysosome contacts. Nat Commun 2022;13:4303. doi: 10.1038/s41467-022-31970-5. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R383] 383.Sun Y, He J, Bao L, Shi X, Wang J, Li Q. Harnessing exercise to combat chronic diseases: The role of Drp1-Mediated mitochondrial fission. Front Cell Dev Biol 2025;13:1481756. doi: 10.3389/fcell.2025.1481756. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R384] 384.Gu C, Yan J, Zhao L, Wu G, Wang YL. Regulation of mitochondrial dynamics by aerobic exercise in cardiovascular diseases. Front Cardiovasc Med 2021;8:788505. doi: 10.3389/fcvm.2021.788505. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R385] 385.Ma M, Chen W, Hua Y, Jia H, Song Y, Wang Y. Aerobic exercise ameliorates cardiac hypertrophy by regulating mitochondrial quality control and endoplasmic reticulum stress through M(2) AChR. J Cell Physiol 2021;236:6581-6596. doi: 10.1002/jcp.30342. [DOI] [PubMed] [Google Scholar]

[R386] 386.Bauer BL, Rochon K, Liu JC, Ramachandran R, Mears JA. Disease-associated mutations in Drp1 have fundamentally different effects on the mitochondrial fission machinery. Hum Mol Genet 2023;32:1975-1987. doi: 10.1093/hmg/ddad029. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R387] 387.Jin JY, Wei XX, Zhi XL, Wang XH, Meng D. Drp1-dependent mitochondrial fission in cardiovascular disease. Acta Pharmacol Sin 2021;42:655-664. doi: 10.1038/s41401-020-00518-y. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R388] 388.Zerihun M, Sukumaran S, Qvit N. The Drp1-mediated mitochondrial fission protein interactome as an emerging core player in mitochondrial dynamics and cardiovascular disease therapy. Int J Mol Sci 2023;24:5785. doi: 10.3390/ijms24065785. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R389] 389.Lv ZM, Liu C, Wang P, Chen YH. Dysregulation of mitochondrial dynamics and mitophagy are involved in high-fat diet-induced steroidogenesis inhibition. J Lipid Res 2024;65:100639. doi: 10.1016/j.jlr.2024.100639. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R390] 390.Tu B Song K Zhou Y Sun H Liu ZY Lin LC, et al. METTL3 boosts mitochondrial fission and induces cardiac fibrosis by enhancing LncRNA GAS5 methylation. Pharmacol Res 2023;194:106840. doi: 10.1016/j.phrs.2023.106840. [DOI] [PubMed] [Google Scholar]

[R391] 391.Si M Chen J Yu R Lin H Li F Jung S, et al. Protein kinase ROCK1 activates mitochondrial fission linking to oxidative stress and muscle atrophy. Kidney Int 2025;108:626-641. doi: 10.1016/j.kint.2025.05.019. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R392] 392.Wadan AS Shaaban AH El-Sadek MZ Mostafa SA Moshref AS El-Hussein A, et al. Mitochondrial-based therapies for neurodegenerative diseases: A review of the current literature. Naunyn Schmiedebergs Arch Pharmacol 2025;398:11357-11386. doi: 10.1007/s00210-025-04014-0. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R393] 393.Curtis WM, Seeds WA, Mattson MP, Bradshaw PC. NADPH and mitochondrial quality control as targets for a circadian-based fasting and exercise therapy for the treatment of Parkinson’s disease. Cells 2022;11:2416. doi: 10.3390/cells11152416. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R394] 394.Zhang J, Qiao W, Luo Y. Mitochondrial quality control proteases and their modulation for cancer therapy. Med Res Rev 2023;43:399-436. doi: 10.1002/med.21929. [DOI] [PubMed] [Google Scholar]

[R395] 395.Wu L, Wang L, Du Y, Zhang Y, Ren J. Mitochondrial quality control mechanisms as therapeutic targets in doxorubicin-induced cardiotoxicity. Trends Pharmacol Sci 2023;44:34-49. doi: 10.1016/j.tips.2022.10.003. [DOI] [PubMed] [Google Scholar]

[R396] 396.Li W Zhang Y Wei Y Ling G Zhang Y Li Y, et al. New insights into mitochondrial quality control in anthracycline-induced cardiotoxicity: Molecular mechanisms, therapeutic targets, and natural products. Int J Biol Sci 2025;21:507-523. doi: 10.7150/ijbs.103810. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R397] 397.Bai Y, Wu J, Yang Z, Wang X, Zhang D, Ma J. Mitochondrial quality control in cardiac ischemia/reperfusion injury: New insights into mechanisms and implications. Cell Biol Toxicol 2023;39:33-51. doi: 10.1007/s10565-022-09716-2. [DOI] [PubMed] [Google Scholar]

[R398] 398.Ye W Han K Xie M Li S Chen G Wang Y, et al. Mitochondrial energy metabolism in diabetic cardiomyopathy: Physiological adaption, pathogenesis, and therapeutic targets. Chin Med J 2024;137:936-948. doi: 10.1097/CM9.0000000000003075. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R399] 399.Zhang T Wang L Duan X Niu Y Li M Yun L, et al. Sirtuins mediate mitochondrial quality control mechanisms: A novel therapeutic target for osteoporosis. Front Endocrinol (Lausanne) 2023;14:1281213. doi: 10.3389/fendo.2023.1281213. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R400] 400.Liu J Wang J Xiong A Zhang L Zhang Y Liu Y, et al. Mitochondrial quality control in lung diseases: Current research and future directions. Front Physiol 2023;14:1236651. doi: 10.3389/fphys.2023.1236651. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R401] 401.Xu M, Feng P, Yan J, Li L. Mitochondrial quality control: A pathophysiological mechanism and potential therapeutic target for chronic obstructive pulmonary disease. Front Pharmacol 2024;15:1474310. doi: 10.3389/fphar.2024.1474310. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R402] 402.Yao C, Li Z, Sun K, Zhang Y, Shou S, Jin H. Mitochondrial dysfunction in acute kidney injury. Ren Fail 2024;46:2393262. doi: 10.1080/0886022X.2024.2393262. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R403] 403.Chen L Yang J Cai Z Huang Y Zhang Q Zhou C, et al. Cerium dioxide nanoparticles-based inspector enhances mitochondrial quality control to maintain chondrocyte homeostasis in osteoarthritis therapy. Adv Healthc Mater 2025;14:e2405069. doi: 10.1002/adhm.202405069. [DOI] [PubMed] [Google Scholar]

[R404] 404.Jia L, Yang Y, Sun F, Tao H, Lu C, Yang JJ. Mitochondrial quality control in liver fibrosis: Epigenetic hallmarks and therapeutic strategies. Cell Signal 2024;115:111035. doi: 10.1016/j.cellsig.2024.111035. [DOI] [PubMed] [Google Scholar]

[R405] 405.Sharafi F, Rismani E, Rhmanian M, Khosravi A, Zarrabi A, Vosough M. Mitochondrial dysfunction in hepatocellular carcinoma: From metabolism to targeted therapies. Mol Cell Biochem 2025;480:6015-6038. doi: 10.1007/s11010-025-05377-x. [DOI] [PubMed] [Google Scholar]

[R406] 406.Wang L, Zhou X, Lu T. Role of mitochondria in physiological activities, diseases, and therapy. Mol Biomed 2025;6:42. doi: 10.1186/s43556-025-00284-5. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R407] 407.Hou D Liu R Hao S Dou Y Chen G Liu L, et al. Notoginsenoside R1 improves intestinal microvascular functioning in sepsis by targeting Drp1-mediated mitochondrial quality imbalance. Pharm Biol 2024;62:250-260. doi: 10.1080/13880209.2024.2318349. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R408] 408.Tian L Jia Z Yan Y Jia Q Shi W Cui S, et al. Low-dose of caffeine alleviates high altitude pulmonary edema via regulating mitochondrial quality control process in AT1 cells. Front Pharmacol 2023;14:1155414. doi: 10.3389/fphar.2023.1155414. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R409] 409.Son YS Kwon YH Lee MS Kwon O Jeong YJ Mun SJ, et al. Helicobacter pylori VacA-induced mitochondrial damage in the gastric pit cells of the antrum and therapeutic rescue. Biomaterials 2025;314:122842. doi: 10.1016/j.biomaterials.2024.122842. [DOI] [PubMed] [Google Scholar]

[R410] 410.Jang HJ, Kim YY, Lee KM, Shin JE, Yun J. The PINK1 activator niclosamide mitigates mitochondrial dysfunction and thermal hypersensitivity in a paclitaxel-induced drosophila model of peripheral neuropathy. Biomedicines 2022;10:863. doi: 10.3390/biomedicines10040863. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R411] 411.Feng Y Goncalves MM Jitkova Y Keszei AFA Yan Y Sarathy C, et al. Serine phosphorylation facilitates protein degradation by the human mitochondrial ClpXP protease. Proc Natl Acad Sci U S A 2025;122:e2422447122. doi: 10.1073/pnas.2422447122. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R412] 412.Cen X, Xu X, Xia H. Targeting MCL1 to induce mitophagy is a potential therapeutic strategy for Alzheimer disease. Autophagy 2021;17:818-819. doi: 10.1080/15548627.2020.1860542. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R413] 413.Dong Y Zhuang XX Wang YT Tan J Feng D Li M, et al. Chemical mitophagy modulators: Drug development strategies and novel regulatory mechanisms. Pharmacol Res 2023;194:106835. doi: 10.1016/j.phrs.2023.106835. [DOI] [PubMed] [Google Scholar]

[R414] 414.Rodriguez YA, Kaur S, Nolte E, Zheng Z, Blagg BSJ, Dobrowsky RT. Novologue therapy requires heat shock protein 70 and thioredoxin-interacting protein to improve mitochondrial bioenergetics and decrease mitophagy in diabetic sensory neurons. ACS Chem Neurosci 2021;12:3049-3059. doi: 10.1021/acschemneuro.1c00340. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R415] 415.Palabiyik AA, Palabiyik E. Pharmacological approaches to enhance mitochondrial biogenesis: Focus on PGC-1Alpha, AMPK, and SIRT1 in cellular health. Mol Biol Rep 2025;52:270. doi: 10.1007/s11033-025-10368-8. [DOI] [PubMed] [Google Scholar]

[R416] 416.Zhong YL Xu CQ Li J Liang ZQ Wang MM Ma C, et al. Mitochondrial dynamics and metabolism in macrophages for cardiovascular disease: A review. Phytomedicine 2025;140:156620. doi: 10.1016/j.phymed.2025.156620. [DOI] [PubMed] [Google Scholar]

[R417] 417.Kong L Liu Y Wang JH Lv MJ Wang YZ Sun WP, et al. Linggui Zhugan decoction ameliorating mitochondrial damage of doxorubicin-induced cardiotoxicity by modulating the AMPK-FOXO3a pathway targeting BTG2. Phytomedicine 2025;139:156529. doi: 10.1016/j.phymed.2025.156529. [DOI] [PubMed] [Google Scholar]

[R418] 418.Lee JY, Lim W, Song G. Tumor-suppressive function of methiothepin in human placental choriocarcinoma cells. Reproduction 2020;160:919-929. doi: 10.1530/REP-20-0377. [DOI] [PubMed] [Google Scholar]

[R419] 419.Cerqueira FM Kozer N Petcherski A Baranovski BM Wolf D Assali EA, et al. MitoTimer-based high-content screen identifies two chemically-related benzothiophene derivatives that enhance basal mitophagy. Biochem J 2020;477:461-475. doi: 10.1042/BCJ20190616. [DOI] [PubMed] [Google Scholar]

[R420] 420.Kodam P, Kumar V, Pattanayak P, Vitta P, Chatterjee T, Maity S. Novel small molecule derivatives improve survivability in the cellular model of Huntington’s disease via improving mitochondrial fusion. RSC Med Chem 2025;17:705-722. doi: 10.1039/d5md00345h. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R421] 421.Gubic S Hendrickx LA Toplak Z Sterle M Peigneur S Tomasic T, et al. Discovery of K(V) 1.3 ion channel inhibitors: Medicinal chemistry approaches and challenges. Med Res Rev 2021;41:2423-2473. doi: 10.1002/med.21800. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R422] 422.Kazi NH, Klink N, Gallant K, Kipka GM, Gersch M. Chimeric deubiquitinase engineering reveals structural basis for specific inhibition of the mitophagy regulator USP30. Nat Struct Mol Biol 2025;32:1776-1786. doi: 10.1038/s41594-025-01534-4. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R423] 423.Ren Y Wu LL Song W Gao Y Shao L Lu Z, et al. Mitochondrial electron flow dynamics imaging for assessing mitochondrial quality and drug screening. Adv Sci (Weinh) 2025;12:e2410561. doi: 10.1002/advs.202410561. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R424] 424.Debnath P. Organic fluorophores conjugated with pyridinium acceptor: A Review on design, synthesis, and application in mitochondrial imaging. Curr Pharm Des 2026;32:971-1001. doi: 10.2174/0113816128395084250708080830. [DOI] [PubMed] [Google Scholar]

[R425] 425.Qiao J, Liu Y, Ma Z, Zhao X, Feng Y. Quantifying mitochondrial viscosity changes by an AIE probe during drug therapy. Chem Commun (Camb) 2025;61:11037-11040. doi: 10.1039/d5cc01021g. [DOI] [PubMed] [Google Scholar]

[R426] 426.Feng X, Cai W, Li Q, Zhao L, Meng Y, Xu H. Activation of lysosomal Ca2+ channels mitigates mitochondrial damage and oxidative stress. J Cell Biol 2025;224:e202403104. doi: 10.1083/jcb.202403104. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R427] 427.Liu M, Ji W, Zhao X, Liu X, Hu JF, Cui J. Therapeutic potential of engineering the mitochondrial genome. Biochim Biophys Acta Mol Basis Dis 2023;1869:166804. doi: 10.1016/j.bbadis.2023.166804. [DOI] [PubMed] [Google Scholar]

[R428] 428.Falabella M, Minczuk M, Hanna MG, Viscomi C, Pitceathly RDS. Gene therapy for primary mitochondrial diseases: Experimental advances and clinical challenges. Nat Rev Neurol 2022;18:689-698. doi: 10.1038/s41582-022-00715-9. [DOI] [PubMed] [Google Scholar]

[R429] 429.Tang JX, Pyle A, Taylor RW, Olahova M. Interrogating mitochondrial biology and disease using CRISPR/Cas9 gene editing. Genes (Basel) 2021;12:1604. doi: 10.3390/genes12101604. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R430] 430.Wang Y, Wang Y, Chen Y, Yan Q, Lin A. Research progress in mitochondrial gene editing technology (in Chinese). Journal of Zhejiang University (Medical Sciences) 2023;52:460-472. doi: 10.3724/zdxbyxb-2023-0129. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R431] 431.Gao Y, Guo L, Wang F, Wang Y, Li P, Zhang D. Development of mitochondrial gene-editing strategies and their potential applications in mitochondrial hereditary diseases: A review. Cytotherapy 2024;26:11-24. doi: 10.1016/j.jcyt.2023.10.004. [DOI] [PubMed] [Google Scholar]

[R432] 432.Slone J, Huang T. The special considerations of gene therapy for mitochondrial diseases. NPJ Genom Med 2020;5:7. doi: 10.1038/s41525-020-0116-5. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R433] 433.Guo Y Zhang K Gao X Zhou Z Liu Z Yang K, et al. Sustained oligomycin sensitivity conferring protein expression in cardiomyocytes protects against cardiac hypertrophy induced by pressure overload via improving mitochondrial function. Hum Gene Ther 2020;31:1178-1189. doi: 10.1089/hum.2020.004. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R434] 434.Keshavan N Greenwood M Prunty H Diaz JA Privolizzi R Counsell J, et al. Gene therapy prevents hepatic mitochondrial dysfunction in murine deoxyguanosine kinase deficiency. Mol Ther Methods Clin Dev 2025;33:101397. doi: 10.1016/j.omtm.2024.101397. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R435] 435.Pares M Fornaguera C Vila-Julia F Oh S Fan SHY Tam YK, et al. Preclinical assessment of a gene-editing approach in a mouse model of mitochondrial neurogastrointestinal encephalomyopathy. Hum Gene Ther 2021;32:1210-1223. doi: 10.1089/hum.2021.152. [DOI] [PubMed] [Google Scholar]

[R436] 436.Cho YW, Yoon J, Song SG, Noh YW. Mitochondrial DNA as a target for analyzing the biodistribution of cell therapy products. Sci Rep 2024;14:7934. doi: 10.1038/s41598-024-56591-4. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R437] 437.Zhang X Huang L Li C Yang J Duan F Su Q, et al. Gene therapy prevents onset of mitochondrial cardiomyopathy in neonatal mice with Ndufs6 deficiency. Cell Death Discov 2025;11:249. doi: 10.1038/s41420-025-02524-7. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R438] 438.Li H Sun B Huang Y Zhang J Xu X Shen Y, et al. Gene therapy of yeast NDI1 on mitochondrial complex I dysfunction in rotenone-induced Parkinson’s disease models in vitro and vivo. Mol Med 2022;28:29. doi: 10.1186/s10020-022-00456-x. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R439] 439.Li H Chen Z Shen Y Xiong T Chen A Chen L, et al. Gene therapy in Abeta-induced cell and mouse models of Alzheimer’s disease through compensating defective mitochondrial complex I function. J Transl Med 2024;22:760. doi: 10.1186/s12967-024-05571-3. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R440] 440.Chemello F Pozzobon M Tsansizi LI Varanita T Quintana-Cabrera R Bonesso D, et al. Dysfunctional mitochondria accumulate in a skeletal muscle knockout model of Smn1, the causal gene of spinal muscular atrophy. Cell Death Dis 2023;14:162. doi: 10.1038/s41419-023-05573-x. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R441] 441.She M Huang M Zhang J Yan Y Zhou L Zhang M, et al. Astragulus embranaceus (Fisch.) Bge-Dioscorea opposita Thunb herb pair ameliorates sarcopenia in senile type 2 diabetes mellitus through Rab5a/mTOR-mediated mitochondrial dysfunction. J Ethnopharmacol 2023;317:116737. doi: 10.1016/j.jep.2023.116737. [DOI] [PubMed] [Google Scholar]

[R442] 442.Base editing ablates all protein-coding genes of the mitochondrial genome in mouse cells. Nat Biomed Eng 2023;7:614-615. doi: 10.1038/s41551-022-00986-z. [DOI] [PubMed] [Google Scholar]

[R443] 443.Hanaford AR, Cho YJ, Nakai H. AAV-vector based gene therapy for mitochondrial disease: Progress and future perspectives. Orphanet J Rare Dis 2022;17:217. doi: 10.1186/s13023-022-02324-7. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R444] 444.Na JH, Lee YM. Therapeutic approach to epilepsy in patients with mitochondrial diseases. Yonsei Med J 2025;66:131-140. doi: 10.3349/ymj.2024.0325. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R445] 445.Nishida R Nukaga S Kawahara I Miyagawa Y Goto K Nakashima C, et al. Differential effects of three medium-chain fatty acids on mitochondrial quality control and skeletal muscle maturation. Antioxidants (Basel) 2024;13:821. doi: 10.3390/antiox13070821. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R446] 446.Azzolino D Bertoni C De Cosmi V Spolidoro GCI Agostoni C Lucchi T, et al. Omega-3 polyunsatured fatty acids and physical performance across the lifespan: A narrative review. Front Nutr 2024;11:1414132. doi: 10.3389/fnut.2024.1414132. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R447] 447.Wang Y Sun J Xue L Sun Y Zhang K Fan M, et al. Chlorogenic acid improves high-fat diet-induced skeletal muscle metabolic disorders by regulating mitochondrial function and lactate metabolism. J Agric Food Chem 2025;73:10347-10357. doi: 10.1021/acs.jafc.5c03967. [DOI] [PubMed] [Google Scholar]

[R448] 448.Cheng K Yao J Song Z Huang J Zhao H Yang R, et al. Effects of resveratrol on redox status, jejunal injury, and mitochondrial function in intrauterine growth-retarded weaned piglets. Animals (Basel) 2025;15:290. doi: 10.3390/ani15030290. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R449] 449.Nederveen JP Mastrolonardo AJ Xhuti D Di Carlo A Manta K Fuda MR, et al. Novel multi-ingredient supplement facilitates weight loss and improves body composition in overweight and obese individuals: A randomized, double-blind, placebo-controlled clinical trial. Nutrients 2023;15:3693. doi: 10.3390/nu15173693. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R450] 450.Mercurio G Giacco A Scopigno N Vigliotti M Goglia F Cioffi F, et al. Mitochondria at the crossroads: Linking the mediterranean diet to metabolic health and non-pharmacological approaches to NAFLD. Nutrients 2025;17:1214. doi: 10.3390/nu17071214. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R451] 451.You Y Ni H Ma Q Jiang L Cai J He W, et al. Ketogenic diet ameliorates MASLD via balancing mitochondrial dynamics and improving mitochondrial dysfunction. Nutr Diabetes 2025;15:37. doi: 10.1038/s41387-025-00391-w. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R452] 452.Na JH, Kim HD, Lee YM. Effective and safe diet therapies for Lennox-Gastaut syndrome with mitochondrial dysfunction. Ther Adv Neurol Disord 2020;13:1756286419897813. doi: 10.1177/1756286419897813. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R453] 453.Dzotsi M Strohm A Varshney S Zuniga-Hertz JP Chitteti R Manoogian E, et al. Time-restricted eating improves quality of life, heart rate, and mitochondrial function in patients with postural orthostatic tachycardia syndrome. medRxiv 2025:2025.05.29.25328448. doi: 10.1101/2025.05.29.25328448. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R454] 454.Tomtheelnganbee E, Sah P, Sharma R. Mitochondrial function and nutrient sensing pathways in ageing: Enhancing longevity through dietary interventions. Biogerontology 2022;23:657-680. doi: 10.1007/s10522-022-09978-7. [DOI] [PubMed] [Google Scholar]

[R455] 455.Widjaja S, Antarianto RD, Hardiany NS. Effects of dietary restriction on PGC-1alpha regulation in the development of age-associated diseases. Curr Aging Sci 2024;17:189-195. doi: 10.2174/0118746098301226240402051508. [DOI] [PubMed] [Google Scholar]

[R456] 456.Fuentes-Barria H Aguilera-Eguia R Angarita-Davila L Rojas-Gomez D Alarcon-Rivera M Lopez-Soto O, et al. Vitamin D and sarcopenia: Implications for muscle health. Biomedicines 2025;13:1863. doi: 10.3390/biomedicines13081863. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R457] 457.Killilea DW, Killilea AN. Mineral requirements for mitochondrial function: A connection to redox balance and cellular differentiation. Free Radic Biol Med 2022;182:182-191. doi: 10.1016/j.freeradbiomed.2022.02.022. [DOI] [PubMed] [Google Scholar]

[R458] 458.Choi SE Hwang Y Lee SJ Jung H Shin TH Son Y, et al. Mitochondrial protease ClpP supplementation ameliorates diet-induced NASH in mice. J Hepatol 2022;77:735-747. doi: 10.1016/j.jhep.2022.03.034. [DOI] [PubMed] [Google Scholar]

[R459] 459.Liu S Faitg J Tissot C Konstantopoulos D Laws R Bourdier G, et al. Urolithin A provides cardioprotection and mitochondrial quality enhancement preclinically and improves human cardiovascular health biomarkers. iScience 2025;28: 111814. doi: 10.1016/j.isci.2025.111814. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R460] 460.Broome SC, Whitfield J, Karagounis LG, Hawley JA. Mitochondria as nutritional targets to maintain muscle health and physical function during ageing. Sports Med 2024;54:2291-2309. doi: 10.1007/s40279-024-02072-7. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R461] 461.Handayani D, Handayani A, Rudijanto A, Nuraissa P, Rahmawati W, Huang XF. Effects of brown rice, meal replacements, and anti-obesity drugs on mitochondria in obese rats. Diabetes Metab Syndr Obes 2025;18:3151-3165. doi: 10.2147/DMSO.S535983. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R462] 462.Nagpal D, Nema S, Nagpal S, Pandey MM, Kaushik D, Kathuria H. Management and prevention of neurodegenerative disorders: Can antioxidant-rich dietary interventions help? Antioxidants (Basel) 2025;14:1078. doi: 10.3390/antiox14091078. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R463] 463.Jun L, Tao YX, Geetha T, Babu JR. Mitochondrial adaptation in skeletal muscle: Impact of obesity, caloric restriction, and dietary compounds. Curr Nutr Rep 2024;13:500-515. doi: 10.1007/s13668-024-00555-7. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R464] 464.Prem PN, Kurian GA. High-fat diet increased oxidative stress and mitochondrial dysfunction induced by renal ischemia-reperfusion injury in rat. Front Physiol 2021;12:715693. doi: 10.3389/fphys.2021.715693. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R465] 465.Han X Zhang B Gong Q Liu T Wang C Sun Y, et al. The tolerable upper intake level of manganese alleviates Parkinson-like motor performance and neuronal loss by activating mitophagy. Free Radic Biol Med 2024;225:665-676. doi: 10.1016/j.freeradbiomed.2024.10.281. [DOI] [PubMed] [Google Scholar]

[R466] 466.Lima MR, Moreira BJ, Bertuzzi R, Lima-Silva AE. Could nanotechnology improve exercise performance? Evidence from animal studies. Braz J Med Biol Res 2024;57:e13360. doi: 10.1590/1414-431X2024e13360. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R467] 467.Golpour-Hamedani S, Bagherniy M, Khorvash F, Feizi A, Sharma M, Askari G. Investigating the effects of co-supplementation with alpha-linolenic acid and L-carnitine on inflammatory status, oxidative stress, clinical symptoms, mental health and quality of life in women with migraine: A protocol for a randomized, triple-blind, placebo-controlled trial. Trials 2024;25:666. doi: 10.1186/s13063-024-08500-3. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R468] 468.Jiao Q, Xiang L, Chen Y. Mitochondrial transplantation: A promising therapy for mitochondrial disorders. Int J Pharm 2024;658:124194. doi: 10.1016/j.ijpharm.2024.124194. [DOI] [PubMed] [Google Scholar]

[R469] 469.Chernyak BV. Mitochondrial transplantation: A critical analysis. Biochemistry (Mosc) 2020;85:636-641. doi: 10.1134/S0006297920050132. [DOI] [PubMed] [Google Scholar]

[R470] 470.Cao M Zou J Shi M Zhao D Liu C Liu Y, et al. A promising therapeutic: Exosome-mediated mitochondrial transplantation. Int Immunopharmacol 2024;142:113104. doi: 10.1016/j.intimp.2024.113104. [DOI] [PubMed] [Google Scholar]

[R471] 471.Nakano T, Irie K, Matsuo K, Mishima K, Nakamura Y. Molecular and cellular mechanisms of mitochondria transfer in models of central nervous system disease. J Cereb Blood Flow Metab 2026;46:269-288. doi: 10.1177/0271678X241300223. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R472] 472.Lim GB. Intracoronary mitochondrial transplantation. Nat Rev Cardiol 2020;17:131. doi: 10.1038/s41569-020-0340-9. [DOI] [PubMed] [Google Scholar]

[R473] 473.Doulamis IP, McCully JD. Mitochondrial transplantation for ischemia reperfusion injury. Methods Mol Biol 2021;2277:15-37. doi: 10.1007/978-1-0716-1270-5_2. [DOI] [PubMed] [Google Scholar]

[R474] 474.Wang LJ Guo PF Zhang S Wang S Chen YZ Yan HW, et al. Mitochondrial transfer/transplantation in lung injury: Mechanism, therapeutic potential, and clinical application. Front Immunol 2025;16:1668281. doi: 10.3389/fimmu.2025.1668281. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R475] 475.Iwata K, Noguchi M, Shintani N. Mitochondrial transplantation in animal models of psychiatric disorders: A novel approach to psychiatric treatment. Biomolecules 2025;15:184. doi: 10.3390/biom15020184. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R476] 476.McCully JD, Del Nido PJ, Emani SM. Mitochondrial transplantation for organ rescue. Mitochondrion 2022;64:27-33. doi: 10.1016/j.mito.2022.02.007. [DOI] [PubMed] [Google Scholar]

[R477] 477.Baharvand F Habibi Roudkenar M Pourmohammadi-Bejarpasi Z Najafi-Ghalehlou N Feizkhah A Bashiri Aliabadi S, et al. Safety and efficacy of platelet-derived mitochondrial transplantation in ischaemic heart disease. Int J Cardiol 2024;410:132227. doi: 10.1016/j.ijcard.2024.132227. [DOI] [PubMed] [Google Scholar]

[R478] 478.Joore IP Shehata S Muffels I Castro-Alpizar J Jimenez-Curiel E Nagyova E, et al. Correction of pathogenic mitochondrial DNA in patient-derived disease models using mitochondrial base editors. PLoS Biol 2025;23:e3003207. doi: 10.1371/journal.pbio.3003207. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R479] 479.Lim K. Mitochondrial genome editing: Strategies, challenges, and applications. BMB Rep 2024;57:19-29. doi: 10.5483/BMBRep.2023-0224. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R480] 480.Kubat GB, Ulger O, Akin S. Requirements for successful mitochondrial transplantation. J Biochem Mol Toxicol 2021;35:e22898. doi: 10.1002/jbt.22898. [DOI] [PubMed] [Google Scholar]

[R481] 481.Zhang TG, Miao CY. Mitochondrial transplantation as a promising therapy for mitochondrial diseases. Acta Pharm Sin B 2023;13:1028-1035. doi: 10.1016/j.apsb.2022.10.008. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R482] 482.Toosky M, Kheradvar A. Assessment of mitochondrial viability under calcium stress: Insights for mitochondrial transplantation. Mitochondrion 2025;86:102098. doi: 10.1016/j.mito.2025.102098. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R483] 483.Li M Wu L Si H Wu Y Liu Y Zeng Y, et al. Engineered mitochondria in diseases: Mechanisms, strategies, and applications. Signal Transduct Target Ther 2025;10:71. doi: 10.1038/s41392-024-02081-y. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R484] 484.Bodenstein DF Siebiger G Zhao Y Clasky AJ Mukkala AN Beroncal EL, et al. Bridging the gap between in vitro and in vivo models: A way forward to clinical translation of mitochondrial transplantation in acute disease states. Stem Cell Res Ther 2024;15:157. doi: 10.1186/s13287-024-03771-8. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R485] 485.Wu J, Xu J, Zhang M, Zhong J, Gao W, Wu M. Chondrocyte mitochondrial quality control: A novel insight into osteoarthritis and cartilage regeneration. Adv Wound Care (New Rochelle) 2026;15:50-70. doi: 10.1089/wound.2024.0270. [DOI] [PubMed] [Google Scholar]

[R486] 486.Wu S, Bakky MAH, Zhang M, Tran NT, Li S. Harnessing mitochondrial quality control in oxidative stress and environmental resilience in aquaculture. Vet Res Commun 2026;50:121. doi: 10.1007/s11259-025-11051-w. [DOI] [PubMed] [Google Scholar]

[R487] 487.Liu H Huang S Chen S Liang S Huang M Li S, et al. Pharmacological potential of Chinese botanical drugs in managing chronic kidney disease by targeting mitochondrial quality control. Front Pharmacol 2025;16:1725842. doi: 10.3389/fphar.2025.1725842. [DOI] [PMC free article] [PubMed] [Google Scholar]

PERMALINK

Mitochondrial quality control in health and disease: Updates 2026

Zhengzhao Liu

Wenbao Hu

Lin Sun

Huafeng Liu

Abstract

Introduction

Figure 1.

Mechanisms of MQC

Mitochondrial biogenesis

Figure 2.

Mitochondrial dynamics (fusion and fission)

Figure 3.

Mitophagy

Figure 4.

Mitochondrial proteostasis

Figure 5.

Mitochondria-derived vesicles

Figure 6.

Nuclear–mitochondria crosstalk in genome maintenance and signaling

Other important mechanisms regulating mitochondrial function

The Role of MQC in Health

Maintaining cellular energy metabolism

Antioxidant and anti-apoptotic effects

Imbalance of MQC and Its Association with Diseases

MQC and neurodegenerative diseases

MQC and cardiovascular diseases

MQC and acute and chronic kidney diseases

MQC and metabolic diseases

MQC and tumors

Table 1.

Targeted MQC Therapeutic Strategies

Enhancing mitophagy

Inhibition of excessive mitochondrial fission

MQC as a novel therapeutic target: Future research directions and clinical applications

Emerging Therapies Targeting Mitochondrial Dysfunction

Small molecule drugs

Gene therapy

Nutritional interventions

Mitochondrial transplantation

Conclusions and Future Directions

Funding

Conflicts of interest

Footnotes

References

ACTIONS

PERMALINK

RESOURCES

Similar articles

Cited by other articles

Links to NCBI Databases