. 2023 Oct 5;12(10):1311. doi: 10.3390/biology12101311

Table 1.

Characterization and consequences of mitochondrial dysfunction contributing to the development of chronic liver diseases.

Condition	Characterization	Regulation	Abnormalities	References
Hepatic iron overload	Influences the conversion of hydrogen peroxide (H₂O₂) to highly toxic hydroxyl radicals (HO•).	Hepcidin is feedback-regulated by iron concentrations in plasma and the liver and by erythropoietic demand for iron.	ROS accumulation, cytotoxicity and oxidative stress.	[25]
Ferritin overload	Primary intracellular iron storage protein in both prokaryotes and eukaryotes.	Participates in oxidation–reduction, iron ion transport across membranes and cellular iron ion homeostasis.	Hemochromatosis or hemosiderosis.	[26,27]
Chronic iron overload	Enhances iNOS synthase.	Activation of extracellular signal-regulated kinase (ERK1/2) and nuclear transcription factor (NFκB) in the liver.	Liver steatosis and fibrosis.	[28,29]
Ferroptosis	Intracellular iron-dependent form of cell death that is distinct from necrosis and autophagy.	Accumulation of lipid peroxides.	Neurological dysfunction and cell death.	[36]
Voltage-dependent anion channel 1 (VDAC) in outer mitochondrial membrane	Cellular Ca²⁺ homeostasis by mediating the transport of Ca²⁺ in and out of mitochondria. VDAC1 is highly Ca²⁺-permeable and modulates Ca²⁺ access to the mitochondrial intermembrane space.	Mitochondria-mediated apoptosis by the release of apoptotic proteins.	Increase in calcium into the mitochondria leads to apoptosis.	[5,6]
VDAC oligomerization	VDAC oligomerization inducing mitochondrial outer membrane permeabilization causing mtDNA release.	Mitochondrial stress releases mtDNA into the cytosol, thereby triggering the type Ι interferon (IFN) response.	Regulates Ca²⁺ influx, metabolism, inflammasome activation and cell death.	[43]
Mitochondrial calcium uniporter	Transmembrane protein that allows for the passage of calcium ions from cytosol into mitochondria.	Regulated by MICU1 and MICU2 and plays a fundamental role in the shaping of global calcium signaling and in the control of aerobic metabolism, as well as apoptosis.	Oxidative stress-elevated mitochondrial calcium and its function in neurodegenerative disorders. Hepatic lipid accumulation through MCU/PP4/AMPK molecular signaling mechanism.	[8]
Depolarization of the inner mitochondrial membrane mediated	Allows for antioxidant molecules to exit mitochondria, reducing the organelles’ ability to neutralize ROS.	Caspase-mediated apoptosis.	Increased ROS production.	[13]
Paraptosis, a non-apoptotic type of programmed cell death	Non-apoptotic type of programmed cell death.	Fragmentation of DNA and caspase activation, cell death occurring by cytoplasmic vacuolation.	Mitochondrial swelling.	[19]