Dysfunctional Mitochondria Clearance in Situ: Mitophagy in Obesity and Diabetes-Associated Cardiometabolic Diseases

Several mitochondrial dysfunctions in obesity and diabetes include impaired mitochondrial membrane potential, excessive mitochondrial reactive oxygen species generation, reduced mitochondrial DNA, increased mitochondrial Ca2+ flux, and mitochondrial dynamics disorders. Mitophagy, specialized autopha...

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Published in:Diabetes & metabolism journal 2024, 48(4), 204, pp.503-517
Main Authors: Tang, Songling, Hao, Di, Ma, Wen, Liu, Lian, Gao, Jiuyu, Yao, Peng, Yu, Haifang, Gan, Lu, Cao, Yu
Format: Article
Language:English
Subjects:
Animals
Cardiovascular Diseases - etiology
Cardiovascular Diseases - metabolism
diabetes mellitus
Diabetes Mellitus - metabolism
heart diseases
Humans
Membrane Potential, Mitochondrial
Mitochondria - metabolism
Mitophagy
obesity
Obesity - complications
Obesity - metabolism
parkin protein
Protein Kinases - metabolism
pten-induced putative kinase
Reactive Oxygen Species - metabolism
Review
Ubiquitin-Protein Ligases - metabolism
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Summary:Several mitochondrial dysfunctions in obesity and diabetes include impaired mitochondrial membrane potential, excessive mitochondrial reactive oxygen species generation, reduced mitochondrial DNA, increased mitochondrial Ca2+ flux, and mitochondrial dynamics disorders. Mitophagy, specialized autophagy, is responsible for clearing dysfunctional mitochondria in physiological and pathological conditions. As a paradox, inhibition and activation of mitophagy have been observed in obesity and diabetes-related heart disorders, with both exerting bidirectional effects. Suppressed mitophagy is beneficial to mitochondrial homeostasis, also known as benign mitophagy. On the contrary, in most cases, excessive mitophagy is harmful to dysfunctional mitochondria elimination and thus is defined as detrimental mitophagy. In obesity and diabetes, two classical pathways appear to regulate mitophagy, including PTEN-induced putative kinase 1 (PINK1)/Parkin-dependent mitophagy and receptors/adapters-dependent mitophagy. After the pharmacologic interventions of mitophagy, mitochondrial morphology and function have been restored, and cell viability has been further improved. Herein, we summarize the mitochondrial dysfunction and mitophagy alterations in obesity and diabetes, as well as the underlying upstream mechanisms, in order to provide novel therapeutic strategies for the obesity and diabetes-related heart disorders.
ISSN:2233-6079
2233-6087
2233-6087
DOI:10.4093/dmj.2023.0213