Review Article

Drp1-dependent mitochondrial fission in cardiovascular disease

Authors: Jia-yu Jin1, Xiang-xiang Wei1, Xiu-ling Zhi1, Xin-hong Wang1, Dan Meng1
1 Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Shanghai Key Laboratory of Bioactive Small Molecules, Fudan University, Shanghai 200032, China
Correspondence to: Xin-hong Wang: Wangxh@shmu.edu.cn, Dan Meng: dmeng@fudan.edu.cn,
DOI: 10.1038/s41401-020-00518-y
Received: 9 July 2020
Accepted: 19 August 2020
Advance online: 10 September 2020

Abstract

Mitochondria are highly dynamic organelles undergoing cycles of fusion and fission to modulate their morphology, distribution, and function, which are referred as ‘mitochondrial dynamics’. Dynamin-related protein 1 (Drp1) is known as the major pro-fission protein whose activity is tightly regulated to clear the damaged mitochondria via mitophagy, ensuring a strict control over the intricate process of cellular and organ dynamics in heart. Various posttranslational modifications (PTMs) of Drp1 have been identified including phosphorylation, SUMOylation, palmitoylation, ubiquitination, S-nitrosylation, and O-GlcNAcylation, which implicate a role in the regulation of mitochondrial dynamics. An intact mitochondrial homeostasis is critical for heart to fuel contractile function and cardiomyocyte metabolism, while defects in mitochondrial dynamics constitute an essential part of the pathophysiology underlying various cardiovascular diseases (CVDs). In this review, we summarize current knowledge on the critical role of Drp1 in the pathogenesis of CVDs including endothelial dysfunction, smooth muscle remodeling, cardiac hypertrophy, pulmonary arterial hypertension, myocardial ischemia–reperfusion, and myocardial infarction. We also highlight how the targeting of Drp1 could potentially contribute to CVDs treatments.
Keywords: Drp1; mitochondrial fission; cardiovascular diseases; mitophagy; posttranslational modifications

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