11/8/2023 0 Comments Drp1 fissionWe will also highlight how the targeting of Drp1 may potentially contribute to CVD treatment. Hence, we will review current knowledge on the critical role of Drp1 in the pathogenesis of CVDs, including pulmonary arterial hypertension (PAH), heart failure, cardiac hypertrophy, and myocardial infarction (MI). However, all these findings indicate a close relationship between mitochondrial dynamics in CVDs and Drp1-induced mitochondrial fragmentation. Emerging evidence suggests that disrupted mitochondrial dynamics play vital roles in the pathogenesis of many cardiovascular diseases (CVDs), mainly by influencing cellular energy, reactive oxygen species (ROS) generation, intracellular calcium levels, apoptogenic protein production and some other mechanisms in a cell- or tissue-specific manner. Īs a main energy-demanding organ, the heart relies heavily on mitochondrial ATP production to fuel contractile function and cardiomyocyte metabolism. Mitochondrial dynamics processes are regulated by specific proteins, known as mitochondria-shaping proteins, among which the cytosolic GTPase dynamin-related protein 1 (Drp1) is the main pro-fission protein with activity that is tightly controlled to ensure balanced mitochondrial dynamics according to cellular needs. Mitochondrial dynamics has attracted increasing attention over the past decade because of its close interconnection with mitochondrial function. Intriguingly, they are highly dynamic organelles that undergo fusion and fission to regulate their morphology and control their number and size, a process called “mitochondrial dynamics”. Mitochondria are the “power houses” of cells, producing the energy necessary for a myriad of cellular processes. We also highlight how the targeting of Drp1 could potentially contribute to CVDs treatments. 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. 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). 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. 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. Mitochondria are highly dynamic organelles undergoing cycles of fusion and fission to modulate their morphology, distribution, and function, which are referred as ‘mitochondrial dynamics’.
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