Drp1-dependent mitochondrial fission in cardiovascular disease

• 作者: Jia-yu Jin Xiang-xiang Wei Xiu-ling Zhi Xin-hong Wang Dan Meng
• 来源期刊: 中国药理学报（英文版）
• 年，卷（期）: 2021,（5）
• 所属期刊栏目: Review Article
• 页码范围: 655-664
• 页数: 10页
• 语种: 英文

摘要

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-GIcNAcylation,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.