ISSN: 1449-2288International Journal of Biological Sciences
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Int J Biol Sci 2022; 18(14):5276-5290. doi:10.7150/ijbs.75402 This issue Cite
Review
Mitochondrial quality control in diabetic cardiomyopathy: from molecular mechanisms to therapeutic strategies
1. Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
2. Department of Critical Care Medicine, The First School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China.
3. Department of Cardiology, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde), Foshan 528308, Guangdong, China.
*These authors contributed equally to this article.
Abstract
In diabetic cardiomyopathy (DCM), a major diabetic complication, the myocardium is structurally and functionally altered without evidence of coronary artery disease, hypertension or valvular disease. Although numerous anti-diabetic drugs have been applied clinically, specific medicines to prevent DCM progression are unavailable, so the prognosis of DCM remains poor. Mitochondrial ATP production maintains the energetic requirements of cardiomyocytes, whereas mitochondrial dysfunction can induce or aggravate DCM by promoting oxidative stress, dysregulated calcium homeostasis, metabolic reprogramming, abnormal intracellular signaling and mitochondrial apoptosis in cardiomyocytes. In response to mitochondrial dysfunction, the mitochondrial quality control (MQC) system (including mitochondrial fission, fusion, and mitophagy) is activated to repair damaged mitochondria. Physiological mitochondrial fission fragments the network to isolate damaged mitochondria. Mitophagy then allows dysfunctional mitochondria to be engulfed by autophagosomes and degraded in lysosomes. However, abnormal MQC results in excessive mitochondrial fission, impaired mitochondrial fusion and delayed mitophagy, causing fragmented mitochondria to accumulate in cardiomyocytes. In this review, we summarize the molecular mechanisms of MQC and discuss how pathological MQC contributes to DCM development. We then present promising therapeutic approaches to improve MQC and prevent DCM progression.
Keywords: Diabetic cardiomyopathy, mitochondrial quality control, mitochondrial fission, mitochondrial fusion, mitophagy
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