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Role of mitochondrial dynamics in diabetic cardiomyopathy and regulatory mechanisms

YUE Huan^1,2, DE De-Ma³, DING Ming-Ge³, FU Feng^2,*

¹School of Life Sciences, Northwestern University, Xi’an 710069, China；²Department of Physiology and Pathophysiology, Air Force Medical University, Xi’an 710032, China；³Department of Geriatric Cardiology, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China

Abstract

Cardiovascular complications are the leading cause of death in diabetic patients. Among them, diabetic cardiomyopathy (DCM) is a type of specific cardiomyopathy excluding myocardial damage caused by hypertension and coronary heart disease. It is characterized by abnormal metabolism of cardiomyocytes and gradual decline of cardiac function. The clinical manifestations of DCM are impaired diastolic function in early stage and impaired systolic function in late stage. Eventually it developed into heart failure. Mitochondria are the main organelles that provide energy in cardiomyocytes. Mitochondrial dynamics refers to the dynamic process of mitochondrial fusion and fission, which is an important approach for mitochondrial quality control. Mitochondrial dynamics plays a crucial role in maintaining mitochondrial homeostasis and cardiac function. The proteins that regulate mitochondrial fission are mainly Drp1 and its receptors, Fis1, MFF, MiD49 and MiD51. The protein that performs mitochondrial outer membrane fusion is Mfn1/2, and the inner membrane fusion protein is Opa1. This paper reviews recent progress on mitochondrial dynamics in DCM. The main contents are as follows: mitochondrial dynamics imbalance in both type 1 and 2 DCM is manifested as increased fission and inhibited fusion. The molecular mechanism of the former is mainly associated with up-regulated Drp1 and down-regulated Opa1, while the molecular mechanism of the latter is mainly associated with up-regulated Drp1 and down-regulated Mfn1/2. Increased mitochondrial fission and inhibited fusion can lead to mitochondrial dysfunction and promote the development of DCM. The active ingredients of the traditional Chinese medicine such as punicalagin, paeonol and endogenous substance melatonin can improve mitochondrial function and alleviate the symptoms of DCM by inhibiting mitochondrial fission or promoting mitochondrial fusion. This article is helpful to further understand the role and mechanism of mitochondrial dynamics in DCM, and provide new treatment methods and intervention strategies for clinical DCM patients based on mitochondrial dynamics.

Key words: diabetic cardiomyopathy; mitochondrial dynamics; mitochondrial fusion; mitochondrial fission; mitochondrial function; transcription; post-translational modification

Received: 　　Accepted:

Corresponding author: 付锋　　E-mail: fufeng048@126.com

DOI: 10.13294/j.aps.2024.0012

Citing This Article：

YUE Huan, DE De-Ma, DING Ming-Ge, FU Feng. Role of mitochondrial dynamics in diabetic cardiomyopathy and regulatory mechanisms. Acta Physiol Sin 2024; 76 (1): 128-136 (in Chinese with English abstract).