1Department of Emergency Medicine, Laboratory of Emergency Medicine, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, China
2Sichuan University-The Hong Kong Polytechnic University Institute for Disaster Management and Reconstruction, Chengdu, China
3Disaster Medical Center, Sichuan University, Chengdu, China
Copyright © 2024 Korean Diabetes Association
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Diseases | Mitochondrial dysfunction | Changes of mitophagy | Mitophagy evaluation | Effects of mitophagy | Mitophagy intervention | Reference |
---|---|---|---|---|---|---|
Diabetic cardiomyopathy | Decreased ATP synthesis, lower ΔΨm, increased mtROS, increased mtD-NA, mitochondrial calcium | Inhibition | LC3B, p62, mt-Keima | Reduced apoptosis, inflammation, mitochondrial apoptosis, and ER stress | Activation by Parkin overexpression, inhibition by FUNDC1 ablation | [6,7] |
Diabetic kidney disease | Impaired mitochondrial dynamics, lower ΔΨm, increased mtROS, increased mtDNA | Inhibition | TEM, LC3B+VDAC/TOM20/COX-IV, p62 | Reduced ROS production, apoptosis, reduced RTEC senescence, alleviated EMT, and fibrosis | Inhibition by OPTN siRNA, inhibition by PHB2 deletion | [15,22,23,65] |
Obesity-related NAFLD; hepatic steatosis | Decreased ATP synthesis, impaired mitochondrial dynamics, lower ΔΨm, the increased opening rate of mPTP, increased mtROS | Inhibition | LC3B (mito-LC3B), TOM20+LAMP1 | Decreased markers of liver damage, repressed hepatic lipogenesis and fibrosis, attenuated hepatocyte ROS, inflammation, and apoptosis | Inhibition by Parkin siRNA or Parkin ablation, inhibition by Bnip3 knockdown | [18,38,70] |
Painful diabetic neuropathy | Lower ΔΨm | Inhibition | TEM, LC3B+COX-IV, COX-IV+LAMP1 | Decreased cellular ROS and apoptosis | Inhibition by lysosome deacidificant (DC661) | [41] |
Diabetic retinopathy | Lower ΔΨm, increased mtROS | Inhibition; activation | TEM, GFP-LC3+MitoTracker, p62 | Increased proliferation, decreased inflammation and mitochondrial apoptosis | Activation by PINK1/Parkin overexpression, inhibition by PINK1 siRNA | [57] |
Diabetic hyposalivation | Increased mitochondrial volume, decreased ATP synthesis, lower ΔΨm, decreased mtDNA | Activation | TEM, LC3B, p62, mitochondria and lysosome markers | Improved morphology and secretion of SMG | None | [17] |
Diseases | Mitochondrial dysfunction | Changes of mitophagy | Mitophagy evaluation | Effects of mitophagy | Mitophagy intervention | Reference |
---|---|---|---|---|---|---|
Obesity-exposed oocytes | Decreased ATP synthesis, lower ΔΨm | Activation | PINK1 | Failure in the conversion from fertilized oocytes to the blastocyst stage in oocytes | None | [42] |
Obesity-induced cardiomyopathy | Decreased ATP synthesis, reduced mitochondrial mass, decreased mtDNA | Activation | TEM, LC3B+TOM20, TOM20+LAMP1, mt-Keima | Increased cardiac dysfunction | Inhibition by PINK1 siRNA | [16] |
Diabetic osteoporosis | Reduced intracellular Mg2+ | Activation | TEM, LC3B, p62, PINK1, Parkin | Impaired osteogenic capability | Inhibition by Parkin-RNAi | [74] |
Diabetic nephropathy | Decreased ATP synthesis, impaired mitochondrial dynamics, increased mtROS | Activation | LC3B, p62, BNIP3 | Not mentioned | None | [43] |
Diabetes-related depression | Lower ΔΨm, increased mtROS | Activation | GFP-LC3, mRFP-LC3, beclin 1, Parkin | Enhanced apoptosis, exacerbated depressionlike behavior | Activation by rapamycin, inhibition by MHY1485 | [44] |
Diabetic retinopathy | Mitochondrial morphology alterations | Activation then inhibition | Mitophagy-reporter mice, FL-Pink1/ΔN-Pink1 ratio, LC3B+COX-IV | Increased cellular senescence | None | [8] |
ATP, adenosine triphosphate; mtROS, mitochondrial reactive oxygen species; mtDNA, mitochondrial DNA; LC3B, microtubule-associated protein 1 light chain 3 beta; ER, endoplasmic reticulum; FUNDC1, FUN14 domain containing 1; TEM, transmission electron microscope; VDAC, voltage-dependent anion channel; TOM20, translocase of the outer mitochondrial membrane 20; COX-IV, cytochrome c oxidase subunit 4; ROS, reactive oxygen species; RTEC, renal tubular epithelial cell; EMT, epithelial-mesenchymal transition; OPTN, optineurin; siRNA, small interfering RNA; PHB2, prohibitin 2; NAFLD, non-alcoholic fatty liver disease; mPTP, mitochondrial permeability transition pore; LAMP1, lysosomal associated membrane protein 1; Bnip3, BCL2 interacting protein 3; DC661, the lysosome deacidificant; GFP-LC3, green fluorescent protein-light chain 3; PINK1, PTEN-induced putative kinase 1; SMG, submandibular gland.
ATP, adenosine triphosphate; PINK1, PTEN-induced putative kinase 1; mtDNA, mitochondrial DNA; TEM, transmission electron microscope; LC3B, microtubule-associated protein 1 light chain 3 beta; TOM20, translocase of the outer mitochondrial membrane 20; LAMP1, lysosomal associated membrane protein 1; siRNA, small interfering RNA; mtROS, mitochondrial reactive oxygen species; BNIP3, BCL2 interacting protein 3; GFP-LC3, green fluorescent protein-light chain 3; mRFP-LC3, monomeric red fluorescent protein-light chain 3; MHY1485, the mTOR receptor agonist; FL-Pink1, full-length PINK1; ΔN-Pink1, N-terminal–cleaved PINK1; COX-IV, cytochrome c oxidase subunit 4.