Drp1-dependent mitochondrial fission in cardiovascular disease

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.

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Fig. 1: Schematic illustration of Drp1 structure and distribution of posttranslational modifications in cardiomyocytes/hearts.
Fig. 2: Graphical abstract of the role of SUMOylation in Drp1-dependent mitochondrial dynamics.
Fig. 3: Role of DRP1 in mitochondrial dynamics under cardiac stress.

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Acknowledgements

This work was supported by the Shanghai Science and Technology Commission of China (19JC1411300 to DM), Program of Shanghai Academic/Technology Research Leader (20XD1400600 to DM), General Programs (81873469, 81670450 to DM, 81873536 to XHW, 81572713 to XLZ), and the Great Program (91639103 to DM) of the National Natural Science Foundation of China, the National Key R&D Program of China (2018YFC2000202), the funding of Innovative Research Team of High-level Local Universities in Shanghai, a Key Laboratory Program of the Shanghai Municipal Education Commission (ZDSYS14005).

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Correspondence to Xin-hong Wang or Dan Meng.

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Jin, J., Wei, X., Zhi, X. et al. Drp1-dependent mitochondrial fission in cardiovascular disease. Acta Pharmacol Sin (2020). https://doi.org/10.1038/s41401-020-00518-y

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Keywords

  • Drp1
  • mitochondrial fission
  • cardiovascular diseases
  • mitophagy
  • posttranslational modifications

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