Table 3.

Renal cell-type-specific mitoepigenetic vulnerabilities.

Cell type	Mitochondrial vulnerability	Epigenetic/RNA signal	Pathological phenotype	Candidate intervention
Proximal tubular epithelial cell	High OXPHOS/FAO demand; ATP loss and defective mitophagy	SIRT1/PGC-1α suppression, Klotho methylation, miR-21	Failed repair, cytokine release, fibrosis	PGC-1α/FAO restoration; targeted mitochondrial antioxidants (9, 31, 71)
Podocyte	mtROS compromises cytoskeleton and filtration barrier	miR-34a/miR-21 and apoptosis-linked transcription	Proteinuria and glomerulosclerosis	ROS control and apoptosis modulation (41, 66)
Endothelial cell	Hypoxia-sensitive mitochondrial signaling	Inflammatory enhancer activation and nitric oxide pathway changes	Capillary rarefaction, leukocyte recruitment	Endothelial-protective metabolic and anti-inflammatory strategies (53, 87)
Fibroblast/myofibroblast	Metabolic reprogramming supports matrix production	EZH2, HDAC activity, profibrotic methylation	ECM accumulation and scarring	Fibroblast-selective epigenetic modulation (39, 68, 75)
Immune cells	Immunometabolic shift toward inflammatory glycolysis/ROS	NF-κB chromatin priming, ncRNA regulation	Persistent inflammation and fibrosis amplification	Macrophage/T-cell immunometabolic targeting (19, 59)
Mesangial cell	Hyperglycemia-associated mtROS generation, impaired mitochondrial respiration, and metabolic reprogramming toward a matrix-producing phenotype	TGF-β-responsive miR-192 signaling, with associated miRNA and chromatin changes that reinforce profibrotic gene expression	Mesangial proliferation, increased collagen and fibronectin synthesis, mesangial matrix expansion, and progressive glomerulosclerosis	Reduction of mitochondrial ROS, restoration of metabolic homeostasis, and selective modulation of the TGF-β/Smad–miR-192 axis (20, 25, 41, 88)