Mitochondrial Quality Control in Health and Disease

Abstract

Mitochondria are central regulators of cellular energy metabolism, and their functional integrity is essential for maintaining cellular homeostasis. Mitochondrial quality control (MQC) encompasses a coordinated network of mitochondrial biogenesis, dynamics (fusion and fission), and selective autophagy (mitophagy), which together sustain mitochondrial structure and function. Under physiological conditions, MQC ensures the removal of dysfunctional mitochondria, restricts excessive reactive oxygen species production, and modulates apoptosis, thereby supporting the high energy demands of organs such as the heart and brain. Disruption of MQC contributes to the onset and progression of various diseases, including neurodegenerative disorders, cardiovascular pathologies, and metabolic syndromes, largely through accumulation of damaged mitochondria and impaired metabolic signaling. While the core components of MQC have been characterized, the mechanistic interplay among its modules and their disease-specific alterations remain incompletely defined. This review provides an integrated overview of the molecular pathways governing mitochondrial biogenesis, dynamics, and mitophagy, with a focus on their cross-talk in maintaining mitochondrial homeostasis. We further discuss how MQC dysfunction contributes to disease pathogenesis and examine emerging therapeutic approaches aimed at restoring mitochondrial quality. Understanding the regulatory logic of MQC not only elucidates fundamental principles of cellular stress adaptation but also informs novel strategies for disease intervention.

Keywords

disease intervention / mitochondria / mitochondrial quality control / therapeutic strategies

References

[1] H. L. Glover, A. Schreiner, G. Dewson, S. W. G. Tait, “Mitochondria and Cell Death,” Nature Cell Biology 26, no. 9 (2024): 1434-1446.

[2] H. Wen, H. Deng, B. Li, et al., “Mitochondrial Diseases: From Molecular Mechanisms to Therapeutic Advances,” Signal Transduction and Targeted Therapy 10, no. 1 (2025): 9.

[3] J. Nunnari, A. Suomalainen, “Mitochondria: In Sickness and in Health,” Cell 148, no. 6 (2012): 1145-1159.

[4] G. Ashrafi, T. L. Schwarz, “The Pathways of Mitophagy for Quality Control and Clearance of Mitochondria,” Cell Death and Differentiation 20, no. 1 (2013): 31-42.

[5] F. J. Bock, S. W. G. Tait, “Mitochondria as Multifaceted Regulators of Cell Death,” Nature Reviews Molecular Cell Biology 21, no. 2 (2020): 85-100.

[6] B.-H. Liu, C.-Z. Xu, Y. Liu, et al., “Mitochondrial Quality Control in Human Health and Disease,” Military Medical Research 11, no. 1 (2024): 32.

[7] M. Surma, K. Anbarasu, S. Dutta, et al., “Enhanced Mitochondrial Biogenesis Promotes Neuroprotection in Human Pluripotent Stem Cell Derived Retinal Ganglion Cells,” Communications Biology 6, no. 1 (2023): 218.

[8] W. Wen, H. Zheng, W. Li, et al., “Transcription Factor EB: A Potential Integrated Network Regulator in Metabolic-Associated Cardiac Injury,” Metabolism: Clinical and Experimental 147 (2023): 155662.

[9] L. Qian, Y. Zhu, C. Deng, et al., “Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1 (PGC-1) Family in Physiological and Pathophysiological Process and Diseases,” Signal Transduction and Targeted Therapy 9, no. 1 (2024): 50.

[10] Y.-Q. Li, Y. Jiao, Y.-N. Liu, J.-Y. Fu, L.-K. Sun, J. Su, “PGC-1α Protects From Myocardial Ischaemia-Reperfusion Injury by Regulating Mitonuclear Communication,” Journal of Cellular and Molecular Medicine 26, no. 3 (2022): 593-600.

[11] J. Lumpuy-Castillo, I. Amador-Martínez, M. Díaz-Rojas, et al., “Role of Mitochondria in Reno-Cardiac Diseases: A Study of Bioenergetics, Biogenesis, and GSH Signaling in Disease Transition,” Redox Biology 76 (2024): 103340.

[12] I. Suntar, A. Sureda, T. Belwal, et al., “Natural Products, PGC-1 α, and Duchenne Muscular Dystrophy,” Acta Pharmaceutica Sinica B 10, no. 5 (2020): 734-745.

[13] L. Wang, J. Liu, P. Saha, et al., “The Orphan Nuclear Receptor SHP Regulates PGC-1alpha Expression and Energy Production in Brown Adipocytes,” Cell Metabolism 2, no. 4 (2005): 227-238.

[14] S. Fan, X. Yan, X. Hu, et al., “Shikonin Blocks CAF-Induced TNBC Metastasis by Suppressing Mitochondrial Biogenesis Through GSK-3β/NEDD4-1 Mediated Phosphorylation-Dependent Degradation of PGC-1α,” Journal of Experimental & Clinical Cancer Research : CR 43, no. 1 (2024): 180.

[15] J. Sin, A. M. Andres, D. J. R. Taylor, et al., “Mitophagy Is Required for Mitochondrial Biogenesis and Myogenic Differentiation of C2C12 Myoblasts,” Autophagy 12, no. 2 (2016): 369-380.

[16] X. Qian, X. Li, Z. Shi, et al., “KDM3A Senses Oxygen Availability to Regulate PGC-1α-Mediated Mitochondrial Biogenesis,” Molecular Cell 76, no. 6 (2019): 885-895.e7.

[17] M. Ding, H.-Y. Xu, W.-Y. Zhou, et al., “CLCF1 Signaling Restrains Thermogenesis and Disrupts Metabolic Homeostasis by Inhibiting Mitochondrial Biogenesis in Brown Adipocytes,” Proceedings of the National Academy of Sciences of the United States of America 120, no. 33 (2023): e2305717120.

[18] J. Li, X. Shi, Z. Chen, et al., “Aldehyde Dehydrogenase 2 Alleviates Mitochondrial Dysfunction by Promoting PGC-1α-Mediated Biogenesis in Acute Kidney Injury,” Cell Death & Disease 14, no. 1 (2023): 45.

[19] M. Oláhová, B. Peter, Z. Szilagyi, et al., “POLRMT Mutations Impair Mitochondrial Transcription Causing Neurological Disease,” Nature Communications 12, no. 1 (2021): 1135.

[20] R. C. Scarpulla, “Transcriptional Paradigms in Mammalian Mitochondrial Biogenesis and Function,” Physiological Reviews 88, no. 2 (2008): 611-638.

[21] L. Van Haute, E. O'Connor, H. Díaz-Maldonado, et al., “TEFM Variants Impair Mitochondrial Transcription Causing Childhood-Onset Neurological Disease,” Nature Communications 14, no. 1 (2023): 1009.

[22] N. Desai, H. Yang, V. Chandrasekaran, R. Kazi, M. Minczuk, V. Ramakrishnan, “Elongational Stalling Activates Mitoribosome-Associated Quality Control,” Science (New York, NY) 370, no. 6520 (2020): 1105-1110.

[23] M. Patron, H.-G. Sprenger, T. Langer, “m-AAA Proteases, Mitochondrial Calcium Homeostasis and Neurodegeneration,” Cell Research 28, no. 3 (2018): 296-306.

[24] J. Zhang, W. Qiao, Y. Luo, “Mitochondrial Quality Control Proteases and Their Modulation for Cancer Therapy,” Medicinal Research Reviews 43, no. 2 (2023): 399-436.

[25] R. Gilkerson, H. Kaur, O. Carrillo, I. Ramos, “OMA1-Mediated Mitochondrial Dynamics Balance Organellar Homeostasis Upstream of Cellular Stress Responses,” International Journal of Molecular Sciences 25, no. 8 (2024): 4566.

[26] J. M. Quiles, Å. B. Gustafsson, “The Role of Mitochondrial Fission in Cardiovascular Health and Disease,” Nature Reviews Cardiology 19, no. 11 (2022): 723-736.

[27] L.-C. Tábara, M. Segawa, J. Prudent, “Molecular Mechanisms of Mitochondrial Dynamics,” Nature Reviews Molecular Cell Biology 26, no. 2 (2024): 123-146.

[28] M. D. Pokharel, A. Garcia-Flores, D. Marciano, et al., “Mitochondrial Network Dynamics in Pulmonary Disease: Bridging the Gap Between Inflammation, Oxidative Stress, and Bioenergetics,” Redox Biology 70 (2024): 103049.

[29] W.-L. Hong, H. Huang, X. Zeng, C.-Y. Duan, “Targeting Mitochondrial Quality Control: New Therapeutic Strategies for Major Diseases,” Military Medical Research 11, no. 1 (2024): 59.

[30] F. Kraus, K. Roy, T. J. Pucadyil, M. T. Ryan, “Function and Regulation of the Divisome for Mitochondrial Fission,” Nature 590, no. 7844 (2021): 57-66.

[31] M. Zerihun, S. Sukumaran, N. Qvit, “The Drp1-Mediated Mitochondrial Fission Protein Interactome as an Emerging Core Player in Mitochondrial Dynamics and Cardiovascular Disease Therapy,” International Journal of Molecular Sciences 24, no. 6 (2023): 5785.

[32] Y. Yu, X.-D. Peng, X.-J. Qian, et al., “Fis1 Phosphorylation by Met Promotes Mitochondrial Fission and Hepatocellular Carcinoma Metastasis,” Signal Transduction and Targeted Therapy 6, no. 1 (2021): 401.

[33] K. Atkins, A. Dasgupta, K.-H. Chen, J. Mewburn, S. L. Archer, “The Role of Drp1 Adaptor Proteins MiD49 and MiD51 in Mitochondrial Fission: Implications for Human Disease,” Clinical Science (London, England: 1979) 130, no. 21 (2016): 1861-1874.

[34] T. König, H. Nolte, M. J. Aaltonen, et al., “MIROs and DRP1 Drive Mitochondrial-Derived Vesicle Biogenesis and Promote Quality Control,” Nature Cell Biology 23, no. 12 (2021): 1271-1286.

[35] A. Liu, F. Kage, A. F. Abdulkareem, et al., “Fatty Acyl-Coenzyme A Activates Mitochondrial Division Through Oligomerization of MiD49 and MiD51,” Nature Cell Biology 26, no. 5 (2024): 731-744.

[36] J. Pilic, B. Gottschalk, B. Bourgeois, et al., “Hexokinase 1 Forms Rings That Regulate Mitochondrial Fission During Energy Stress,” Molecular Cell 84, no. 14 (2024): 2732-2746.e5.

[37] J.-Y. Jin, X.-X. Wei, X.-L. Zhi, X.-H. Wang, D. Meng, “Drp1-Dependent Mitochondrial Fission in Cardiovascular Disease,” Acta Pharmacologica Sinica 42, no. 5 (2021): 655-664.

[38] P. Das, O. Chakrabarti, “ISGylation of DRP1 Closely Balances Other Post-Translational Modifications to Mediate Mitochondrial Fission,” Cell Death & Disease 15, no. 3 (2024): 184.

[39] K. Tsushima, H. Bugger, A. R. Wende, et al., “Mitochondrial Reactive Oxygen Species in Lipotoxic Hearts Induce Post-Translational Modifications of AKAP121, DRP1, and OPA1 That Promote Mitochondrial Fission,” Circulation Research 122, no. 1 (2018): 58-73.

[40] J. Huang, P. Xie, Y. Dong, W. An, “Inhibition of Drp1 SUMOylation by ALR Protects the Liver From Ischemia-Reperfusion Injury,” Cell Death and Differentiation 28, no. 4 (2021): 1174-1192.

[41] J.-H. Zhu, S.-X. Ouyang, G.-Y. Zhang, et al., “GSDME Promotes MASLD by Regulating Pyroptosis, Drp1 Citrullination-Dependent Mitochondrial Dynamic, and Energy Balance in Intestine and Liver,” Cell Death and Differentiation 31, no. 11 (2024): 1467-1486.

[42] T. Kleele, T. Rey, J. Winter, et al., “Distinct Fission Signatures Predict Mitochondrial Degradation or Biogenesis,” Nature 593, no. 7859 (2021): 435-439.

[43] C. Duan, R. Liu, L. Kuang, et al., “Activated Drp1 Initiates the Formation of Endoplasmic Reticulum-Mitochondrial Contacts via Shrm4-Mediated Actin Bundling,” Advanced Science (Weinheim, Baden-Wurttemberg, Germany) 10, no. 36 (2023): e2304885.

[44] W.-K. Ji, A. L. Hatch, R. A. Merrill, S. Strack, H. N. Higgs, “Actin Filaments Target the Oligomeric Maturation of the Dynamin GTPase Drp1 to Mitochondrial Fission Sites,” Elife 4 (2015): e11553.

[45] S. Sun, W. Yu, H. Xu, et al., “TBC1D15-Drp1 Interaction-Mediated Mitochondrial Homeostasis Confers Cardioprotection Against Myocardial Ischemia/Reperfusion Injury,” Metabolism: Clinical and Experimental 134 (2022): 155239.

[46] X. Ma, W.-X. Ding, “Quality Control of Mitochondria Involves Lysosomes in Multiple Definitive Ways,” Autophagy 20, no. 12 (2024): 2599-2601.

[47] M. Tong, R. Mukai, S. Mareedu, et al., “Distinct Roles of DRP1 in Conventional and Alternative Mitophagy in Obesity Cardiomyopathy,” Circulation Research 133, no. 1 (2023): 6-21.

[48] M. Song, K. Mihara, Y. Chen, L. Scorrano, G. W. Dorn, “Mitochondrial Fission and Fusion Factors Reciprocally Orchestrate Mitophagic Culling in Mouse Hearts and Cultured Fibroblasts,” Cell Metabolism 21, no. 2 (2015): 273-286.

[49] R. J. Youle, A. M. van der Bliek, “Mitochondrial Fission, Fusion, and Stress,” Science (New York, NY) 337, no. 6098 (2012): 1062-1065.

[50] S. Gao, J. Hu, “Mitochondrial Fusion: The Machineries in and Out,” Trends in Cell Biology 31, no. 1 (2021): 62-74.

[51] R. Quintana-Cabrera, L. Scorrano, “Determinants and Outcomes of Mitochondrial Dynamics,” Molecular Cell 83, no. 6 (2023): 857-876.

[52] M. Ding, R. Shi, S. Cheng, et al., “Mfn2-Mediated Mitochondrial Fusion Alleviates Doxorubicin-Induced Cardiotoxicity With Enhancing Its Anticancer Activity Through Metabolic Switch,” Redox Biology 52 (2022): 102311.

[53] H. Grel, D. Woznica, K. Ratajczak, et al., “Mitochondrial Dynamics in Neurodegenerative Diseases: Unraveling the Role of Fusion and Fission Processes,” International Journal of Molecular Sciences 24, no. 17 (2023): 13033.

[54] M. Zaman, T. E. Shutt, “The Role of Impaired Mitochondrial Dynamics in MFN2-Mediated Pathology,” Frontiers In Cell and Developmental Biology 10 (2022): 858286.

[55] S. Li, S. Han, Q. Zhang, et al., “FUNDC2 Promotes Liver Tumorigenesis by Inhibiting MFN1-Mediated Mitochondrial Fusion,” Nature Communications 13, no. 1 (2022): 3486.

[56] C. Liu, Y. Han, X. Gu, et al., “Paeonol Promotes Opa1-Mediated Mitochondrial Fusion via Activating the CK2α-Stat3 Pathway in Diabetic Cardiomyopathy,” Redox Biology 46 (2021): 102098.

[57] H. Lee, T. J. Lee, C. A. Galloway, et al., “The Mitochondrial Fusion Protein OPA1 Is Dispensable in the Liver and Its Absence Induces Mitohormesis to Protect Liver From Drug-Induced Injury,” Nature Communications 14, no. 1 (2023): 6721.

[58] L. C. Tábara, S. P. Burr, M. Frison, et al., “MTFP1 Controls Mitochondrial Fusion to Regulate Inner Membrane Quality Control and Maintain mtDNA Levels,” Cell 187, no. 14 (2024): 3619-3637.e27.

[59] L. Da Dalt, A. Moregola, M. Svecla, et al., “The Inhibition of Inner Mitochondrial Fusion in Hepatocytes Reduces Non-Alcoholic Fatty Liver and Improves Metabolic Profile During Obesity by Modulating Bile Acid Conjugation,” Cardiovascular Research 119, no. 18 (2024): 2917-2929.

[60] T. Tyagi, T. O. Yarovinsky, E. V. S. Faustino, J. Hwa, “Platelet Mitochondrial Fusion and Function in Vascular Integrity,” Circulation Research 134, no. 2 (2024): 162-164.

[61] S. M. V. Kochan, M. C. Malo, M. Jevtic, et al., “Enhanced Mitochondrial Fusion During a Critical Period of Synaptic Plasticity in Adult-Born Neurons,” Neuron 112, no. 12 (2024): 1997-2014.e6.

[62] M. Sato, K. Sato, “Degradation of Paternal Mitochondria by Fertilization-Triggered Autophagy in C. Elegans Embryos,” Science (New York, NY) 334, no. 6059 (2011): 1141-1144.

[63] K. H. Wrighton, “Development: Autophagy Eliminates Paternal Mitochondria,” Nature Reviews Molecular Cell Biology 12, no. 12 (2011): 771.

[64] E. Doménech, C. Maestre, L. Esteban-Martínez, et al., “AMPK and PFKFB3 Mediate Glycolysis and Survival in Response to Mitophagy During Mitotic Arrest,” Nature Cell Biology 17, no. 10 (2015): 1304-1316.

[65] K. Palikaras, E. Lionaki, N. Tavernarakis, “Mechanisms of Mitophagy in Cellular Homeostasis, Physiology and Pathology,” Nature Cell Biology 20, no. 9 (2018): 1013-1022.

[66] L. Liu, K. Sakakibara, Q. Chen, K. Okamoto, “Receptor-Mediated Mitophagy in Yeast and Mammalian Systems,” Cell Research 24, no. 7 (2014): 787-795.

[67] C. Tang, J. Cai, X.-M. Yin, J. M. Weinberg, M. A. Venkatachalam, Z. Dong, “Mitochondrial Quality Control in Kidney Injury and Repair,” Nature Reviews Nephrology 17, no. 5 (2021): 299-318.

[68] L. A. Kane, M. Lazarou, A. I. Fogel, et al., “PINK1 Phosphorylates Ubiquitin to Activate Parkin E3 Ubiquitin Ligase Activity,” The Journal of Cell Biology 205, no. 2 (2014): 143-153.

[69] J. M. Heo, A. Ordureau, S. Swarup, et al., “RAB7A Phosphorylation by TBK1 Promotes Mitophagy via the PINK-PARKIN Pathway,” Science Advances 4, no. 11 (2018): eaav0443.

[70] Y. Chen, G. W. Dorn, “PINK1-Phosphorylated Mitofusin 2 Is a Parkin Receptor for Culling Damaged Mitochondria,” Science (New York, NY) 340, no. 6131 (2013): 471-475.

[71] M. E. Gegg, J. M. Cooper, K.-Y. Chau, M. Rojo, A. H. V. Schapira, J.-W. Taanman, “Mitofusin 1 and Mitofusin 2 Are Ubiquitinated in a PINK1/Parkin-Dependent Manner Upon Induction of Mitophagy,” Human Molecular Genetics 19, no. 24 (2010): 4861-4870.

[72] M. Lazarou, D. A. Sliter, L. A. Kane, et al., “The Ubiquitin Kinase PINK1 Recruits Autophagy Receptors to Induce Mitophagy,” Nature 524, no. 7565 (2015): 309-314.

[73] G.-L. McLelland, V. Soubannier, C. X. Chen, H. M. McBride, E. A. Fon, “Parkin and PINK1 Function in a Vesicular Trafficking Pathway Regulating Mitochondrial Quality Control,” The EMBO Journal 33, no. 4 (2014): 282-295.

[74] W. Zhu, F. Liu, L. Wang, et al., “pPolyHb Protects Myocardial H9C2 Cells Against Ischemia-Reperfusion Injury by Regulating the Pink1-Parkin-Mediated Mitochondrial Autophagy Pathway. Artificial Cells,” Nanomedicine, and Biotechnology 47, no. 1 (2019): 1248-1255.

[75] Q. Xu, S. Liu, Q. Gong, et al., “Notch1 Protects Against Ischemic-Reperfusion Injury by Suppressing PTEN-Pink1-Mediated Mitochondrial Dysfunction and Mitophagy,” Cells 12, no. 1 (2022): 137.

[76] E. Li, X. Li, J. Huang, et al., “BMAL1 Regulates Mitochondrial Fission and Mitophagy Through Mitochondrial Protein BNIP3 and Is Critical in the Development of Dilated Cardiomyopathy,” Protein & Cell 11, no. 9 (2020): 661-679.

[77] S. C. da Silva Rosa, M. D. Martens, J. T. Field, et al., “BNIP3L/Nix-Induced Mitochondrial Fission, Mitophagy, and Impaired Myocyte Glucose Uptake Are Abrogated by PRKA/PKA Phosphorylation,” Autophagy 17, no. 9 (2021): 2257-2272.

[78] M. Yazdankhah, S. Ghosh, P. Shang, et al., “BNIP3L-Mediated Mitophagy Is Required for Mitochondrial Remodeling During the Differentiation of Optic Nerve Oligodendrocytes,” Autophagy 17, no. 10 (2021): 3140-3159.

[79] M. Chen, Z. Chen, Y. Wang, et al., “Mitophagy Receptor FUNDC1 Regulates Mitochondrial Dynamics and Mitophagy,” Autophagy 12, no. 4 (2016): 689-702.

[80] Y. Xu, J. Shen, Z. Ran, “Emerging Views of Mitophagy in Immunity and Autoimmune Diseases,” Autophagy 16, no. 1 (2020): 3-17.

[81] W. Zhang, S. Siraj, R. Zhang, Q. Chen, “Mitophagy Receptor FUNDC1 Regulates Mitochondrial Homeostasis and Protects the Heart From I/R Injury,” Autophagy 13, no. 6 (2017): 1080-1081.

[82] F. Ding, M. Zhou, Y. Ren, et al., “Mitochondrial Extracellular Vesicles: A Promising Avenue for Diagnosing and Treating Lung Diseases,” ACS Nano 18, no. 37 (2024): 25372-25404.

[83] L. Pei, Z. Yao, D. Liang, K. Yang, L. Tao, “Mitochondria in Skeletal System-Related Diseases,” Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie 181 (2024): 117505.

[84] M. Bueno, J. Calyeca, M. Rojas, A. L. Mora, “Mitochondria Dysfunction and Metabolic Reprogramming as Drivers of Idiopathic Pulmonary Fibrosis,” Redox Biology 33 (2020): 101509.

[85] S. Victorelli, H. Salmonowicz, J. Chapman, et al., “Apoptotic Stress Causes mtDNA Release During Senescence and Drives the SASP,” Nature 622, no. 7983 (2023): 627-636.

[86] M. Y. W. Ng, T. Wai, A. Simonsen, “Quality Control of the Mitochondrion,” Developmental Cell 56, no. 7 (2021): 881-905.

[87] D. C. Chan, “Mitochondrial Dynamics and Its Involvement in Disease,” Annual Review of Pathology 15 (2020): 235-259.

[88] M. Douglas-Escobar, M. D. Weiss, “Hypoxic-Ischemic Encephalopathy: A Review for the Clinician,” JAMA Pediatrics 169, no. 4 (2015): 397-403.

[89] S. K. Dhillon, E. R. Gunn, B. A. Lear, et al., “Cerebral Oxygenation and Metabolism After Hypoxia-Ischemia,” Frontiers In Pediatrics 10 (2022): 925951.

[90] Y. Huan, G. Hao, Z. Shi, Y. Liang, Y. Dong, H. Quan, “The Role of Dynamin-Related Protein 1 in Cerebral Ischemia/Hypoxia Injury,” Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie 165 (2023): 115247.

[91] M. Yang, K. Wang, B. Liu, Y. Shen, G. Liu, “Hypoxic-Ischemic Encephalopathy: Pathogenesis and Promising Therapies,” Molecular Neurobiology 62, no. 2 (2024): 2105-2122.

[92] X.-L. Jiang, Z.-B. Zhang, C.-X. Feng, et al., “PHLDA1 Contributes to Hypoxic Ischemic Brain Injury in Neonatal Rats via Inhibiting FUNDC1-Mediated Mitophagy,” Acta Pharmacologica Sinica 45, no. 9 (2024): 1809-1820.

[93] H. Wen, L. Li, L. Zhan, et al., “Hypoxic Postconditioning Promotes Mitophagy Against Transient Global Cerebral Ischemia via PINK1/Parkin-Induced Mitochondrial Ubiquitination in Adult Rats,” Cell Death & Disease 12, no. 7 (2021): 630.

[94] X.-X. Wang, M. Li, X.-W. Xu, et al., “BNIP3-Mediated Mitophagy Attenuates Hypoxic-Ischemic Brain Damage in Neonatal Rats by Inhibiting Ferroptosis Through P62-KEAP1-NRF2 Pathway Activation to Maintain Iron and Redox Homeostasis,” Acta Pharmacologica Sinica 46, no. 1 (2025): 33-51.

[95] Y. Zhang, D. Chen, Y. Wang, X. Wang, Z. Zhang, Y. Xin, “Neuroprotective Effects of Melatonin-Mediated Mitophagy Through Nucleotide-Binding Oligomerization Domain and Leucine-Rich Repeat-Containing Protein X1 in Neonatal Hypoxic-Ischemic Brain Damage,” FASEB Journal : Official Publication of the Federation of American Societies For Experimental Biology 37, no. 2 (2023): e22784.

[96] J. Zhang, S. Wang, H. Zhang, et al., “Drp1 Acetylation Mediated by CDK5-AMPK-GCN5L1 Axis Promotes Cerebral Ischemic Injury via Facilitating Mitochondrial Fission,” Molecular Medicine (Cambridge, Mass) 30, no. 1 (2024): 173.

[97] Y. Zhang, X. Gong, “Fat Mass and Obesity Associated Protein Inhibits Neuronal Ferroptosis via the FYN/Drp1 Axis and Alleviate Cerebral Ischemia/Reperfusion Injury,” CNS Neuroscience & Therapeutics 30, no. 3 (2024): e14636.

[98] F. G. P. Welt, W. Batchelor, J. R. Spears, et al., “Reperfusion Injury in Patients With Acute Myocardial Infarction: JACC Scientific Statement,” Journal of the American College of Cardiology 83, no. 22 (2024): 2196-2213.

[99] Q. Xiang, X. Yi, X.-H. Zhu, X. Wei, D.-S. Jiang, “Regulated Cell Death in Myocardial Ischemia-Reperfusion Injury,” Trends in Endocrinology and Metabolism: TEM 35, no. 3 (2024): 219-234.

[100] T. Eckle, J. Bertazzo, T. N. Khatua, et al., “Circadian Influences on Myocardial Ischemia-Reperfusion Injury and Heart Failure,” Circulation Research 134, no. 6 (2024): 675-694.

[101] J. Wang, H. Zhou, “Mitochondrial Quality Control Mechanisms as Molecular Targets in Cardiac Ischemia-Reperfusion Injury,” Acta Pharmaceutica Sinica B 10, no. 10 (2020): 1866-1879.

[102] J. Wang, H. Zhuang, L. Jia, 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,” International Journal of Biological Sciences 20, no. 11 (2024): 4458-4475.

[103] H. Ye, J. Lin, H. Zhang, et al., “Nuclear Receptor 4A1 Regulates Mitochondrial Homeostasis in Cardiac Post-Ischemic Injury by Controlling Mitochondrial Fission 1 Protein-Mediated Fragmentation and Parkin-Dependent Mitophagy,” International Journal of Biological Sciences 21, no. 1 (2025): 400-414.

[104] T.-T. Yang, L.-H. Zhou, L.-F. Gu, et al., “CHK1 Attenuates Cardiac Dysfunction via Suppressing SIRT1-Ubiquitination,” Metabolism: Clinical and Experimental 162 (2025): 156048.

[105] M. Chen, G. Zhong, M. Liu, et al., “Integrating Network Analysis and Experimental Validation to Reveal the Mitophagy-Associated Mechanism of Yiqi Huoxue (YQHX) Prescription in the Treatment of Myocardial Ischemia/Reperfusion Injury,” Pharmacological Research 189 (2023): 106682.

[106] L. Chen, Y. Lv, H. Wu, et al., “Gastrodin Exerts Perioperative Myocardial Protection by Improving Mitophagy Through the PINK1/Parkin Pathway to Reduce Myocardial Ischemia-Reperfusion Injury,” Phytomedicine : International Journal of Phytotherapy and Phytopharmacology 133 (2024): 155900.

[107] X. Chang, Q. Zhang, Y. Huang, et al., “Quercetin Inhibits Necroptosis in Cardiomyocytes After Ischemia-Reperfusion via DNA-PKcs-SIRT5-Orchestrated Mitochondrial Quality Control,” Phytotherapy Research: PTR 38, no. 5 (2024): 2496-2517.

[108] Y. Li, Z. Xiong, Y. Jiang, et al., “Klf4 Deficiency Exacerbates Myocardial Ischemia/Reperfusion Injury in Mice via Enhancing ROCK1/DRP1 Pathway-Dependent Mitochondrial Fission,” Journal of Molecular and Cellular Cardiology 174 (2023): 115-132.

[109] X. Niu, J. Zhang, S. Hu, W. Dang, K. Wang, M. Bai, “lncRNA Oip5-as1 Inhibits Excessive Mitochondrial Fission in Myocardial Ischemia/Reperfusion Injury by Modulating DRP1 Phosphorylation,” Cellular & Molecular Biology Letters 29, no. 1 (2024): 72.

[110] S. Su, J. Wang, J. Wang, et al., “Cardioprotective Effects of Gypenoside XVII Against Ischemia/Reperfusion Injury: Role of Endoplasmic Reticulum Stress, Autophagy, and Mitochondrial Fusion Fission Balance,” Phytotherapy Research : PTR 36, no. 7 (2022): 2982-2998.

[111] H. Yu, X. Hong, L. Liu, et al., “Cordycepin Decreases Ischemia/Reperfusion Injury in Diabetic Hearts via Upregulating AMPK/Mfn2-Dependent Mitochondrial Fusion,” Frontiers In Pharmacology 12 (2021): 754005.

[112] Y. Guo, H. Zhang, C. Yan, et al., “Small Molecule Agonist of Mitochondrial Fusion Repairs Mitochondrial Dysfunction,” Nature Chemical Biology 19, no. 4 (2023): 468-477.

[113] A. Pefanis, F. L. Ierino, J. M. Murphy, P. J. Cowan, “Regulated Necrosis in Kidney Ischemia-Reperfusion Injury,” Kidney International 96, no. 2 (2019): 291-301.

[114] H. Zhao, A. Alam, A. P. Soo, A. J. T. George, D. Ma, “Ischemia-Reperfusion Injury Reduces Long Term Renal Graft Survival: Mechanism and Beyond,” EBioMedicine 28 (2018): 31-42.

[115] R. Huang, C. Zhang, Z. Xiang, T. Lin, J. Ling, H. Hu, “Role of Mitochondria in Renal Ischemia-Reperfusion Injury,” The FEBS Journal 291, no. 24 (2024): 5365-5378.

[116] X. Fan, L. Wu, F. Wang, D. Liu, X. Cen, H. Xia, “Mitophagy Regulates Kidney Diseases,” Kidney Diseases (Basel, Switzerland) 10, no. 6 (2024): 573-587.

[117] C. Tang, H. Han, Z. Liu, et al., “Activation of BNIP3-Mediated Mitophagy Protects Against Renal Ischemia-Reperfusion Injury,” Cell Death & Disease 10, no. 9 (2019): 677.

[118] K. A. Hurtado, J. Janda, R. G. Schnellmann, “Lasmiditan Restores Mitochondrial Quality Control Mechanisms and Accelerates Renal Recovery After Ischemia-Reperfusion Injury,” Biochemical Pharmacology 218 (2023): 115855.

[119] M. J. Livingston, J. Wang, J. Zhou, et al., “Clearance of Damaged Mitochondria via Mitophagy Is Important to the Protective Effect of Ischemic Preconditioning in Kidneys,” Autophagy 15, no. 12 (2019): 2142-2162.

[120] Z.-L. Li, L. Ding, R.-X. Ma, et al., “Activation of HIF-1α C-Terminal Transactivation Domain Protects Against Hypoxia-Induced Kidney Injury Through Hexokinase 2-Mediated Mitophagy,” Cell Death & Disease 14, no. 5 (2023): 339.

[121] H. Shi, H. Qi, D. Xie, et al., “Inhibition of ACSF2 Protects Against Renal Ischemia/Reperfusion Injury via Mediating Mitophagy in Proximal Tubular Cells,” Free Radical Biology & Medicine 198 (2023): 68-82.

[122] F. Zhao, J. Zhu, M. Zhang, et al., “OGG1 Aggravates Renal Ischemia-Reperfusion Injury by Repressing PINK1-Mediated Mitophagy,” Cell Proliferation 56, no. 8 (2023): e13418.

[123] L. Su, J. Zhang, J. Wang, et al., “Pannexin 1 Targets Mitophagy to Mediate Renal Ischemia/Reperfusion Injury,” Communications Biology 6, no. 1 (2023): 889.

[124] H. Li, J. Feng, Y. Zhang, et al., “Mst1 Deletion Attenuates Renal Ischaemia-Reperfusion Injury: The Role of Microtubule Cytoskeleton Dynamics, Mitochondrial Fission and the GSK3β-p53 Signalling Pathway,” Redox Biology 20 (2019): 261-274.

[125] Z. Song, Y. Xia, L. Shi, et al., “Inhibition of Drp1- Fis1 Interaction Alleviates Aberrant Mitochondrial Fragmentation and Acute Kidney Injury,” Cellular & Molecular Biology Letters 29, no. 1 (2024): 31.

[126] D. Gu, X. Zou, G. Ju, G. Zhang, E. Bao, Y. Zhu, “Mesenchymal Stromal Cells Derived Extracellular Vesicles Ameliorate Acute Renal Ischemia Reperfusion Injury by Inhibition of Mitochondrial Fission Through miR-30,” Stem Cells Int 2016 (2016): 2093940.

[127] M. Cecconi, L. Evans, M. Levy, A. Rhodes, “Sepsis and Septic Shock,” Lancet (London, England) 392, no. 10141 (2018): 75-87.

[128] D. C. Angus, T. van der Poll, “Severe Sepsis and Septic Shock,” The New England Journal of Medicine 369, no. 9 (2013): 840-851.

[129] F. M. Lira Chavez, L. P. Gartzke, F. E. van Beuningen, et al., “Restoring the Infected Powerhouse: Mitochondrial Quality Control in Sepsis,” Redox Biology 68 (2023): 102968.

[130] M. Mohsin, G. Tabassum, S. Ahmad, S. Ali, M. Ali Syed, “The Role of Mitophagy in Pulmonary Sepsis,” Mitochondrion 59 (2021): 63-75.

[131] T. Jiang, E. Liu, Z. Li, et al., “SIRT1-Rab7 Axis Attenuates NLRP3 and STING Activation Through Late Endosomal-Dependent Mitophagy During Sepsis-Induced Acute Lung Injury,” International Journal of Surgery 110, no. 5 (2024): 2649-2668.

[132] C. Yan, X. Lin, J. Guan, et al., “SIRT3 Deficiency Promotes Lung Endothelial Pyroptosis Through Impairing Mitophagy to Activate NLRP3 Inflammasome During Sepsis-Induced Acute Lung Injury,” Molecular and Cellular Biology 45, no. 1 (2025): 1-16.

[133] F. Liu, Y. Yang, W. Peng, et al., “Mitophagy-Promoting miR-138-5p Promoter Demethylation Inhibits Pyroptosis in Sepsis-Associated Acute Lung Injury,” Inflammation Research: Official Journal of the European Histamine Research Society … [et Al] 72, no. 2 (2023): 329-346.

[134] M. Roden, G. I. Shulman, “The Integrative Biology of Type 2 Diabetes,” Nature 576, no. 7785 (2019): 51-60.

[135] Y. Sun, X. Yao, Q.-J. Zhang, et al., “Beclin-1-Dependent Autophagy Protects the Heart During Sepsis,” Circulation 138, no. 20 (2018): 2247-2262.

[136] X.-X. Zhu, X. Wang, S.-Y. Jiao, et al., “Cardiomyocyte Peroxisome Proliferator-Activated Receptor α Prevents Septic Cardiomyopathy via Improving Mitochondrial Function,” Acta Pharmacologica Sinica 44, no. 11 (2023): 2184-2200.

[137] J. S. Smolen, D. Aletaha, I. B. McInnes, “Rheumatoid Arthritis,” Lancet (London, England) 388, no. 10055 (2016): 2023-2038.

[138] C. Ma, J. Wang, F. Hong, S. Yang, “Mitochondrial Dysfunction in Rheumatoid Arthritis,” Biomolecules 12, no. 9 (2022): 1216.

[139] Z. Hong, H. Wang, T. Zhang, et al., “The HIF-1/BNIP3 Pathway Mediates Mitophagy to Inhibit the Pyroptosis of Fibroblast-Like Synoviocytes in Rheumatoid Arthritis,” International Immunopharmacology 127 (2024): 111378.

[140] Z.-Z. Dai, J. Xu, Q. Zhang, H. Zhou, X.-M. Liu, H. Li, “TREM1 Interferes With Macrophage Mitophagy via the E2F1-Mediated TOMM40 Transcription Axis in Rheumatoid Arthritis,” Free Radical Biology & Medicine 228 (2025): 267-280.

[141] B. Li, C. Yang, M. Guo, et al., “Ultrasound-Remote Selected Activation Mitophagy for Precise Treatment of Rheumatoid Arthritis by Two-Dimensional Piezoelectric Nanosheets,” ACS Nano 17, no. 1 (2023): 621-635.

[142] H. Yao, L. Xiang, Y. Huang, et al., “Guizhi Shaoyao Zhimu Granules Attenuate Bone Destruction in Mice With Collagen-Induced Arthritis by Promoting Mitophagy of Osteoclast Precursors to Inhibit Osteoclastogenesis,” Phytomedicine : International Journal of Phytotherapy and Phytopharmacology 118 (2023): 154967.

[143] H. Lassmann, J. van Horssen, D. Mahad, “Progressive Multiple Sclerosis: Pathology and Pathogenesis,” Nature Reviews Neurology 8, no. 11 (2012): 647-656.

[144] R.-Q. Yao, C. Ren, Z.-F. Xia, Y.-M. Yao, “Organelle-Specific Autophagy in Inflammatory Diseases: A Potential Therapeutic Target Underlying the Quality Control of Multiple Organelles,” Autophagy 17, no. 2 (2021): 385-401.

[145] I. P. de Barcelos, R. M. Troxell, J. S. Graves, “Mitochondrial Dysfunction and Multiple Sclerosis,” Biology 8, no. 2 (2019): 37.

[146] X. Sun, M. Qian, H. Li, et al., “FKBP5 Activates Mitophagy by Ablating PPAR-γ to Shape a Benign Remyelination Environment,” Cell Death & Disease 14, no. 11 (2023): 736.

[147] A. Di Rita, F. Strappazzon, “A Protective Variant of the Autophagy Receptor CALCOCO2/NDP52 in Multiple Sclerosis (MS),” Autophagy 17, no. 6 (2021): 1565-1567.

[148] M. Jucker, L. C. Walker, “Alzheimer's Disease: From Immunotherapy to Immunoprevention,” Cell 186, no. 20 (2023): 4260-4270.

[149] K. C. McGill Percy, Z. Liu, X. Qi, “Mitochondrial Dysfunction in Alzheimer's Disease: Guiding the Path to Targeted Therapies,” Neurotherapeutics: The Journal of the American Society For Experimental NeuroTherapeutics 22, no. 3 (2025): e00525.

[150] E. F. Fang, Y. Hou, K. Palikaras, et al., “Mitophagy Inhibits Amyloid-β and Tau Pathology and Reverses Cognitive Deficits in Models of Alzheimer's Disease,” Nature Neuroscience 22, no. 3 (2019): 401-412.

[151] K. Kingwell, “Turning up Mitophagy in Alzheimer Disease,” Nature Reviews Drug Discovery (2019).

[152] E. F. Fang, “Mitophagy and NAD+ Inhibit Alzheimer Disease,” Autophagy 15, no. 6 (2019): 1112-1114.

[153] Y. Yang, H. Chen, S. Huang, et al., “BOK-Engaged Mitophagy Alleviates Neuropathology in Alzheimer's Disease,” Brain: A Journal of Neurology 148, no. 2 (2025): 432-447.

[154] M. Hou, W. Bao, Y. Gao, J. Chen, G. Song, “Honokiol Improves Cognitive Impairment in APP/PS1 Mice Through Activating Mitophagy and Mitochondrial Unfolded Protein Response,” Chemico-Biological Interactions 351 (2022): 109741.

[155] X. Cen, X. Xu, H. Xia, “Targeting MCL1 to Induce Mitophagy Is a Potential Therapeutic Strategy for Alzheimer Disease,” Autophagy 17, no. 3 (2021): 818-819.

[156] C. Chen, C. Yang, J. Wang, et al., “Melatonin Ameliorates Cognitive Deficits Through Improving Mitophagy in a Mouse Model of Alzheimer's Disease,” Journal of Pineal Research 71, no. 4 (2021): e12774.

[157] E. Tolosa, A. Garrido, S. W. Scholz, W. Poewe, “Challenges in the Diagnosis of Parkinson's Disease,” The Lancet Neurology 20, no. 5 (2021): 385-397.

[158] L. V. Kalia, A. E. Lang, “Parkinson's Disease,” Lancet (London, England) 386, no. 9996 (2015): 896-912.

[159] M. A. Eldeeb, R. A. Thomas, M. A. Ragheb, A. Fallahi, E. A. Fon, “Mitochondrial Quality Control in Health and in Parkinson's Disease,” Physiological Reviews 102, no. 4 (2022): 1721-1755.

[160] T.-S. Z. Fang, Y. Sun, A. C. Pearce, et al., “Knockout or Inhibition of USP30 Protects Dopaminergic Neurons in a Parkinson's Disease Mouse Model,” Nature Communications 14, no. 1 (2023): 7295.

[161] Y. Zhou, Y. Liu, Z. Kang, et al., “CircEPS15, as a Sponge of MIR24-3p Ameliorates Neuronal Damage in Parkinson Disease Through Boosting PINK1-PRKN-Mediated Mitophagy,” Autophagy 19, no. 9 (2023): 2520-2537.

[162] Y. Wang, S. Luo, H. Su, Z. Wang, L. Chu, C. Zhang, “BL-918 Activates PINK1/Parkin Signaling Pathway to Ameliorate the Progression of Parkinson's Disease,” The Journal of Biological Chemistry 300, no. 8 (2024): 107543.

[163] N. Yu, M. Pasha, J. J. E. Chua, “Redox Changes and Cellular Senescence in Alzheimer's Disease,” Redox Biology 70 (2024): 103048.

[164] M. Yang, X. Wei, X. Yi, D.-S. Jiang, “Mitophagy-Related Regulated Cell Death: Molecular Mechanisms and Disease Implications,” Cell Death & Disease 15, no. 7 (2024): 505.

[165] F. R. Palma, B. N. Gantner, M. J. Sakiyama, et al., “ROS Production by Mitochondria: Function or Dysfunction?,” Oncogene 43, no. 5 (2024): 295-303.

[166] D. Nolfi-Donegan, A. Braganza, S. Shiva, “Mitochondrial Electron Transport Chain: Oxidative Phosphorylation, Oxidant Production, and Methods of Measurement,” Redox Biology 37 (2020): 101674.

[167] I. Belenichev, O. Popazova, N. Bukhtiyarova, et al., “Targeting Mitochondrial Dysfunction in Cerebral Ischemia: Advances in Pharmacological Interventions,” Antioxidants (Basel, Switzerland) 14, no. 1 (2025): 108.

[168] X. Wang, M. Li, F. Wang, et al., “TIGAR Reduces Neuronal Ferroptosis by Inhibiting Succinate Dehydrogenase Activity in Cerebral Ischemia,” Free Radical Biology & Medicine 216 (2024): 89-105.

[169] K. Yan, J. Bian, L. He, B. Song, L. Shen, Y. Zhen, “SIRT3 Mitigates Neuroinflammation and Mitochondrial Damage Post-Hypoxic-Ischemic Brain Injury,” Molecular Immunology 179 (2025): 18-28.

[170] T. Zhang, M.-T. He, X.-P. Zhang, L. Jing, J.-Z. Zhang, “Uncoupling Protein 2 Deficiency Enhances NLRP3 Inflammasome Activation Following Hyperglycemia-Induced Exacerbation of Cerebral Ischemia and Reperfusion Damage in Vitro and in Vivo,” Neurochemical Research 46, no. 6 (2021): 1359-1371.

[171] N. Toro-Urrego, J. P. Luaces, T. Kobiec, et al., “Raloxifene Protects Oxygen-Glucose-Deprived Astrocyte Cells Used to Mimic Hypoxic-Ischemic Brain Injury,” International Journal of Molecular Sciences 25, no. 22 (2024): 12121.

[172] G. Chen, Z. Jin, X. Wang, Q.-H. Yu, G.-B. Hu, “Danshen Injection Mitigated the Cerebral Ischemia/Reperfusion Injury by Suppressing Neuroinflammation via the HIF-1α/CXCR4/NF-κB Signaling Pathway,” Neuroreport 35, no. 10 (2024): 601-611.

[173] W. Li, Z. Zhang, J. Li, et al., “Silibinin Exerts Neuroprotective Effects Against Cerebral Hypoxia/Reoxygenation Injury by Activating the GAS6/Axl Pathway,” Toxicology 495 (2023): 153598.

[174] L. Jiang, X. Yin, Y.-H. Chen, et al., “Proteomic Analysis Reveals Ginsenoside Rb1 Attenuates Myocardial Ischemia/Reperfusion Injury Through Inhibiting ROS Production From Mitochondrial Complex I,” Theranostics 11, no. 4 (2021): 1703-1720.

[175] Q. Y. Lu, J. Q. Ma, Y. Y. Duan, et al., “Carthamin Yellow Protects the Heart Against Ischemia/Reperfusion Injury With Reduced Reactive Oxygen Species Release and Inflammatory Response,” Journal of Cardiovascular Pharmacology 74, no. 3 (2019): 228-234.

[176] H. Li, A. Yin, Z. Cheng, et al., “Attenuation of Na/K-ATPase/Src/ROS Amplification Signal Pathway With pNaktide Ameliorates Myocardial Ischemia-Reperfusion Injury,” International Journal of Biological Macromolecules 118, no. Pt A (2018): 1142-1148.

[177] T. Hao, G. Ji, M. Qian, et al., “Intracellular Delivery of Nitric Oxide Enhances the Therapeutic Efficacy of Mesenchymal Stem Cells for Myocardial Infarction,” Science Advances 9, no. 48 (2023): eadi9967.

[178] J. S. Bice, B. R. Jones, G. R. Chamberlain, G. F. Baxter, “Nitric Oxide Treatments as Adjuncts to Reperfusion in Acute Myocardial Infarction: A Systematic Review of Experimental and Clinical Studies,” Basic Research in Cardiology 111, no. 2 (2016): 23.

[179] S. P. Janssens, J. Bogaert, J. Zalewski, et al., “Nitric Oxide for Inhalation in ST-Elevation Myocardial Infarction (NOMI): A Multicentre, Double-Blind, Randomized Controlled Trial,” European Heart Journal 39, no. 29 (2018): 2717-2725.

[180] N. Paolocci, R. Biondi, M. Bettini, et al., “Oxygen Radical-Mediated Reduction in Basal and Agonist-Evoked no Release in Isolated Rat Heart,” Journal of Molecular and Cellular Cardiology 33, no. 4 (2001): 671-679.

[181] T. Hao, M. Qian, Y. Zhang, et al., “An Injectable Dual-Function Hydrogel Protects Against Myocardial Ischemia/Reperfusion Injury by Modulating ROS/NO Disequilibrium,” Advanced Science (Weinheim, Baden-Wurttemberg, Germany) 9, no. 15 (2022): e2105408.

[182] J. Yuan, D. Ofengeim, “A Guide to Cell Death Pathways,” Nature Reviews Molecular Cell Biology 25, no. 5 (2024): 379-395.

[183] G. Eskander, S. G. Abdelhamid, S. A. Wahdan, S. M. Radwan, “Insights on the Crosstalk Among Different Cell Death Mechanisms,” Cell Death Discovery 11, no. 1 (2025): 56.

[184] D. R. Green, “The Coming Decade of Cell Death Research: Five Riddles,” Cell 177, no. 5 (2019): 1094-1107.

[185] X. Tian, P. R. Srinivasan, V. Tajiknia, et al., “Targeting Apoptotic Pathways for Cancer Therapy,” The Journal of Clinical Investigation 134, no. 14 (2024): e179570.

[186] F. Llambi, T. Moldoveanu, S. W. G. Tait, et al., “A Unified Model of Mammalian BCL-2 Protein Family Interactions at the Mitochondria,” Molecular Cell 44, no. 4 (2011): 517-531.

[187] R. J. Youle, A. Strasser, “The BCL-2 Protein Family: Opposing Activities That Mediate Cell Death,” Nature Reviews Molecular Cell Biology 9, no. 1 (2008): 47-59.

[188] Z. Zhou, T. Arroum, X. Luo, et al., “Diverse Functions of Cytochrome c in Cell Death and Disease,” Cell Death and Differentiation 31, no. 4 (2024): 387-404.

[189] C. Purring-Koch, G. McLendon, “Cytochrome c Binding to Apaf-1: The Effects of dATP and Ionic Strength,” Proceedings of the National Academy of Sciences of the United States of America 97, no. 22 (2000): 11928-11931.

[190] D. Bertheloot, E. Latz, B. S. Franklin, “Necroptosis, Pyroptosis and Apoptosis: An Intricate Game of Cell Death,” Cellular & Molecular Immunology 18, no. 5 (2021): 1106-1121.

[191] O. Micheau, J. Tschopp, “Induction of TNF Receptor I-Mediated Apoptosis via Two Sequential Signaling Complexes,” Cell 114, no. 2 (2003): 181-190.

[192] H. Hsu, J. Huang, H. B. Shu, V. Baichwal, D. V. Goeddel, “TNF-Dependent Recruitment of the Protein Kinase RIP to the TNF Receptor-1 Signaling Complex,” Immunity 4, no. 4 (1996): 387-396.

[193] M. J. M. Bertrand, S. Milutinovic, K. M. Dickson, et al., “cIAP1 and cIAP2 Facilitate Cancer Cell Survival by Functioning as E3 Ligases That Promote RIP1 Ubiquitination,” Molecular Cell 30, no. 6 (2008): 689-700.

[194] D. J. Mahoney, H. H. Cheung, R. L. Mrad, et al., “Both cIAP1 and cIAP2 Regulate TNFalpha-Mediated NF-kappaB Activation,” Proceedings of the National Academy of Sciences of the United States of America 105, no. 33 (2008): 11778-11783.

[195] J. Geng, Y. Ito, L. Shi, et al., “Regulation of RIPK1 Activation by TAK1-Mediated Phosphorylation Dictates Apoptosis and Necroptosis,” Nature Communications 8, no. 1 (2017): 359.

[196] A. Degterev, J. Hitomi, M. Germscheid, et al., “Identification of RIP1 Kinase as a Specific Cellular Target of Necrostatins,” Nature Chemical Biology 4, no. 5 (2008): 313-321.

[197] D. Ofengeim, Y. Ito, A. Najafov, et al., “Activation of Necroptosis in Multiple Sclerosis,” Cell Reports 10, no. 11 (2015): 1836-1849.

[198] K. Newton, K. E. Wickliffe, A. Maltzman, et al., “RIPK1 Inhibits ZBP1-Driven Necroptosis During Development,” Nature 540, no. 7631 (2016): 129-133.

[199] X. Zhang, H. Zhang, C. Xu, et al., “Ubiquitination of RIPK1 Suppresses Programmed Cell Death by Regulating RIPK1 Kinase Activation During Embryogenesis,” Nature Communications 10, no. 1 (2019): 4158.

[200] L. Galluzzi, I. Vitale, S. A. Aaronson, et al., “Molecular Mechanisms of Cell Death: Recommendations of the Nomenclature Committee on Cell Death 2018,” Cell Death and Differentiation 25, no. 3 (2018): 486-541.

[201] J. Wan, H. A. Kalpage, A. Vaishnav, et al., “Regulation of Respiration and Apoptosis by Cytochrome c Threonine 58 Phosphorylation,” Scientific Reports 9, no. 1 (2019): 15815.

[202] J. Zhong, H. Ouyang, S. Zheng, et al., “The YAP/SERCA2a Signaling Pathway Protects Cardiomyocytes Against Reperfusion-Induced Apoptosis,” Aging 12, no. 13 (2020): 13618-13632.

[203] X. Yang, M. Zhang, B. Xie, et al., “Myocardial Brain-Derived Neurotrophic Factor Regulates Cardiac Bioenergetics Through the Transcription Factor Yin Yang 1,” Cardiovascular Research 119, no. 2 (2023): 571-586.

[204] H. Hu, J. Nan, Y. Sun, et al., “Electron Leak From NDUFA13 Within Mitochondrial Complex I Attenuates Ischemia-Reperfusion Injury via Dimerized STAT3,” Proceedings of the National Academy of Sciences of the United States of America 114, no. 45 (2017): 11908-11913.

[205] M. Vila-Petroff, M. A. Salas, M. Said, et al., “CaMKII Inhibition Protects Against Necrosis and Apoptosis in Irreversible Ischemia-Reperfusion Injury,” Cardiovascular Research 73, no. 4 (2007): 689-698.

[206] K. Yan, T. An, M. Zhai, et al., “Mitochondrial miR-762 Regulates Apoptosis and Myocardial Infarction by Impairing ND2,” Cell Death & Disease 10, no. 7 (2019): 500.

[207] L. Galluzzi, O. Kepp, F. K.-M. Chan, G. Kroemer, “Necroptosis: Mechanisms and Relevance to Disease,” Annual Review of Pathology 12 (2017): 103-130.

[208] P. Vandenabeele, L. Galluzzi, T. Vanden Berghe, G. Kroemer, “Molecular Mechanisms of Necroptosis: An Ordered Cellular Explosion,” Nature Reviews Molecular Cell Biology 11, no. 10 (2010): 700-714.

[209] H. Zhu, Y. Tan, W. Du, et al., “Phosphoglycerate Mutase 5 Exacerbates Cardiac Ischemia-Reperfusion Injury Through Disrupting Mitochondrial Quality Control,” Redox Biology 38 (2021): 101777.

[210] W. Wang, B. Wang, S. Sun, et al., “Inhibition of Adenosine Kinase Attenuates Myocardial Ischaemia/Reperfusion Injury,” Journal of Cellular and Molecular Medicine 25, no. 6 (2021): 2931-2943.

[211] J. Shi, W. Gao, F. Shao, “Pyroptosis: Gasdermin-Mediated Programmed Necrotic Cell Death,” Trends In Biochemical Sciences 42, no. 4 (2017): 245-254.

[212] P. Yu, X. Zhang, N. Liu, L. Tang, C. Peng, X. Chen, “Pyroptosis: Mechanisms and Diseases,” Signal Transduction and Targeted Therapy 6, no. 1 (2021): 128.

[213] B. E. Burdette, A. N. Esparza, H. Zhu, S. Wang, “Gasdermin D in Pyroptosis,” Acta Pharmaceutica Sinica B 11, no. 9 (2021): 2768-2782.

[214] T. O. Yarovinsky, M. Su, C. Chen, Y. Xiang, W. H. Tang, J. Hwa, “Pyroptosis in Cardiovascular Diseases: Pumping Gasdermin on the Fire,” Seminars in Immunology 69 (2023): 101809.

[215] R. Miao, C. Jiang, W. Y. Chang, et al., “Gasdermin D Permeabilization of Mitochondrial Inner and Outer Membranes Accelerates and Enhances Pyroptosis,” Immunity 56, no. 11 (2023): 2523-2541.e8.

[216] M. Kawaguchi, M. Takahashi, T. Hata, et al., “Inflammasome Activation of Cardiac Fibroblasts Is Essential for Myocardial Ischemia/Reperfusion Injury,” Circulation 123, no. 6 (2011): 594-604.

[217] Ø. Sandanger, T. Ranheim, L. E. Vinge, et al., “The NLRP3 Inflammasome is Up-Regulated in Cardiac Fibroblasts and Mediates Myocardial Ischaemia-Reperfusion Injury,” Cardiovascular Research 99, no. 1 (2013): 164-174.

[218] L. Chen, L.-S. Mao, J.-Y. Xue, et al., “Myocardial Ischemia-Reperfusion Injury: The Balance Mechanism Between Mitophagy and NLRP3 Inflammasome,” Life Sciences 355 (2024): 122998.

[219] Y. Duan, Q. Li, J. Wu, et al., “A Detrimental Role of Endothelial S1PR2 in Cardiac Ischemia-Reperfusion Injury via Modulating Mitochondrial Dysfunction, NLRP3 Inflammasome Activation, and Pyroptosis,” Redox Biology 75 (2024): 103244.

[220] R. Zhou, A. S. Yazdi, P. Menu, J. Tschopp, “A Role for Mitochondria in NLRP3 Inflammasome Activation,” Nature 469, no. 7329 (2011): 221-225.

[221] K. Nakahira, J. A. Haspel, V. A. K. Rathinam, et al., “Autophagy Proteins Regulate Innate Immune Responses by Inhibiting the Release of Mitochondrial DNA Mediated by the NALP3 Inflammasome,” Nature Immunology 12, no. 3 (2011): 222-230.

[222] S. Toldo, E. Mezzaroma, A. G. Mauro, F. Salloum, B. W. Van Tassell, A. Abbate, “The Inflammasome in Myocardial Injury and Cardiac Remodeling,” Antioxidants & Redox Signaling 22, no. 13 (2015): 1146-1161.

[223] M. E. Heid, P. A. Keyel, C. Kamga, S. Shiva, S. C. Watkins, R. D. Salter, “Mitochondrial Reactive Oxygen Species Induces NLRP3-Dependent Lysosomal Damage and Inflammasome Activation,” Journal of Immunology (Baltimore, Md: 1950) 191, no. 10 (2013): 5230-5238.

[224] M. Yabal, D. J. Calleja, D. S. Simpson, K. E. Lawlor, “Stressing out the Mitochondria: Mechanistic Insights Into NLRP3 Inflammasome Activation,” Journal of Leukocyte Biology 105, no. 2 (2019): 377-399.

[225] S. S. Iyer, Q. He, J. R. Janczy, et al., “Mitochondrial Cardiolipin Is Required for Nlrp3 Inflammasome Activation,” Immunity 39, no. 2 (2013): 311-323.

[226] X. Wang, X. Li, S. Liu, et al., “PCSK9 Regulates Pyroptosis via mtDNA Damage in Chronic Myocardial Ischemia,” Basic Research in Cardiology 115, no. 6 (2020): 66.

[227] B. Gan, “Mitochondrial Regulation of Ferroptosis,” The Journal of Cell Biology 220, no. 9 (2021): e202105043.

[228] S. Ahola, T. Langer, “Ferroptosis in Mitochondrial Cardiomyopathy,” Trends in Cell Biology 34, no. 2 (2023): 150-160.

[229] X. Jiang, B. R. Stockwell, M. Conrad, “Ferroptosis: Mechanisms, Biology and Role in Disease,” Nature Reviews Molecular Cell Biology 22, no. 4 (2021): 266-282.

[230] W. Cai, L. Liu, X. Shi, et al., “Alox15/15-HpETE Aggravates Myocardial Ischemia-Reperfusion Injury by Promoting Cardiomyocyte Ferroptosis,” Circulation 147, no. 19 (2023): 1444-1460.

[231] X. Fang, H. Wang, D. Han, et al., “Ferroptosis as a Target for Protection Against Cardiomyopathy,” Proceedings of the National Academy of Sciences of the United States of America 116, no. 7 (2019): 2672-2680.

[232] S. P. Chelko, G. Keceli, A. Carpi, et al., “Exercise Triggers CAPN1-Mediated AIF Truncation, Inducing Myocyte Cell Death in Arrhythmogenic Cardiomyopathy,” Science Translational Medicine 13, no. 581 (2021): eabf0891.

[233] H.-X. Su, L.-L. Xu, P.-B. Li, H.-L. Bi, W.-X. Jiang, H.-H. Li, “Psmb8 Inhibits Mitochondrial Fission and Alleviates Myocardial Ischaemia/Reperfusion Injury by Targeting Drp1 Degradation,” Cell Death & Disease 15, no. 11 (2024): 803.

[234] L. Pham, T. Arroum, J. Wan, et al., “Regulation of Mitochondrial Oxidative Phosphorylation Through Tight Control of Cytochrome c Oxidase in Health and Disease—Implications for Ischemia/Reperfusion Injury, Inflammatory Diseases, Diabetes, and Cancer,” Redox Biology 78 (2024): 103426.

[235] L. R. Barclay, M. R. Vinqvist, “Do Spin Traps Also Act as Classical Chain-Breaking Antioxidants? A Quantitative Kinetic Study of Phenyl Tert-Butylnitrone (PBN) in Solution and in Liposomes,” Free Radical Biology & Medicine 28, no. 7 (2000): 1079-1090.

[236] Y. Kotake, “Pharmacologic Properties of Phenyl N-Tert-Butylnitrone,” Antioxidants & Redox Signaling 1, no. 4 (1999): 481-499.

[237] J. Fauconnier, A. C. Meli, J. Thireau, et al., “Ryanodine Receptor Leak Mediated by Caspase-8 Activation Leads to Left Ventricular Injury After Myocardial Ischemia-Reperfusion,” Proceedings of the National Academy of Sciences of the United States of America 108, no. 32 (2011): 13258-13263.

[238] Y. Tan, D. Mui, S. Toan, P. Zhu, R. Li, H. Zhou, “SERCA Overexpression Improves Mitochondrial Quality Control and Attenuates Cardiac Microvascular Ischemia-Reperfusion Injury,” Molecular Therapy Nucleic Acids 22 (2020): 696-707.

[239] G. W. Dorn, R. B. Vega, D. P. Kelly, “Mitochondrial Biogenesis and Dynamics in the Developing and Diseased Heart,” Genes & Development 29, no. 19 (2015): 1981-1991.

[240] R. Ventura-Clapier, A. Garnier, V. Veksler, “Transcriptional Control of Mitochondrial Biogenesis: The Central Role of PGC-1alpha,” Cardiovascular Research 79, no. 2 (2008): 208-217.

[241] Y. Li, Y.-F. Feng, X.-T. Liu, et al., “Songorine Promotes Cardiac Mitochondrial Biogenesis via Nrf2 Induction During Sepsis,” Redox Biology 38 (2021): 101771.

[242] M. Fontecha-Barriuso, D. Martin-Sanchez, J. M. Martinez-Moreno, et al., “The Role of PGC-1α and Mitochondrial Biogenesis in Kidney Diseases,” Biomolecules 10, no. 2 (2020): 347.

[243] C. Zeng, M. Chen, “Progress in Nonalcoholic Fatty Liver Disease: SIRT Family Regulates Mitochondrial Biogenesis,” Biomolecules 12, no. 8 (2022): 1079.

[244] S. Jamwal, J. K. Blackburn, J. D. Elsworth, “PPARγ/PGC1α Signaling as a Potential Therapeutic Target for Mitochondrial Biogenesis in Neurodegenerative Disorders,” Pharmacology & Therapeutics 219 (2021): 107705.

[245] H. Fan, R. Ding, W. Liu, et al., “Heat Shock Protein 22 Modulates NRF1/TFAM-Dependent Mitochondrial Biogenesis and DRP1-Sparked Mitochondrial Apoptosis Through AMPK-PGC1α Signaling Pathway to Alleviate the Early Brain Injury of Subarachnoid Hemorrhage in Rats,” Redox Biology 40 (2021): 101856.

[246] D. W. B. Piyarathna, A. Balasubramanian, J. M. Arnold, et al., “ERR1 and PGC1α Associated Mitochondrial Alterations Correlate With Pan-Cancer Disparity in African Americans,” The Journal of Clinical Investigation 129, no. 6 (2019): 2351-2356.

[247] Y. Bai, J. Wu, Z. Yang, X. Wang, D. Zhang, J. Ma, “Mitochondrial Quality Control in Cardiac Ischemia/Reperfusion Injury: New Insights Into Mechanisms and Implications,” Cell Biology and Toxicology 39, no. 1 (2023): 33-51.

[248] L. Chen, Y. Qin, B. Liu, et al., “PGC-1α-Mediated Mitochondrial Quality Control: Molecular Mechanisms and Implications for Heart Failure,” Frontiers in Cell and Developmental Biology 10 (2022): 871357.

[249] S. Wan, Z. Cui, L. Wu, et al., “Ginsenoside Rd Promotes Omentin Secretion in Adipose Through TBK1-AMPK to Improve Mitochondrial Biogenesis via WNT5A/Ca2+ Pathways in Heart Failure,” Redox Biology 60 (2023): 102610.

[250] B. Mokhtari, L. Hosseini, P. F. Høilund-Carlsen, R. Salehinasab, M. Rajabi, R. Badalzadeh, “The Additive Effects of Nicotinamide Mononucleotide and Melatonin on Mitochondrial Biogenesis and Fission/Fusion, Autophagy, and microRNA-499 in the Aged Rat Heart With Reperfusion Injury,” Naunyn-Schmiedeberg's Archives of Pharmacology 396, no. 8 (2023): 1701-1711.

[251] L. Wei, X. Sun, X. Qi, Y. Zhang, Y. Li, Y. Xu, “Dihydromyricetin Ameliorates Cardiac Ischemia/Reperfusion Injury Through Sirt3 Activation,” BioMed Research International 2019 (2019): 6803943.

[252] W. A. Basheer, Y. Fu, D. Shimura, et al., “Stress Response Protein GJA1-20k Promotes Mitochondrial Biogenesis, Metabolic Quiescence, and Cardioprotection Against Ischemia/Reperfusion Injury,” JCI Insight 3, no. 20 (2018): e121900.

[253] J. Yang, J. He, M. Ismail, et al., “HDAC Inhibition Induces Autophagy and Mitochondrial Biogenesis to Maintain Mitochondrial Homeostasis During Cardiac Ischemia/Reperfusion Injury,” Journal of Molecular and Cellular Cardiology 130 (2019): 36-48.

[254] G. Karamanlidis, L. Nascimben, G. S. Couper, P. S. Shekar, F. del Monte, R. Tian, “Defective DNA Replication Impairs Mitochondrial Biogenesis in Human Failing Hearts,” Circulation Research 106, no. 9 (2010): 1541-1548.

[255] A. M. Andres, K. C. Tucker, A. Thomas, et al., “Mitophagy and Mitochondrial Biogenesis in Atrial Tissue of Patients Undergoing Heart Surgery With Cardiopulmonary Bypass,” JCI Insight 2, no. 4 (2017): e89303.

RIGHTS & PERMISSIONS

2025 The Author(s). MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.