Mitophagy in cardiovascular diseases: molecular mechanisms, pathogenesis, and treatment

• Published in: Trends in molecular medicine Vol. 28; no. 10; pp. 836 - 849
• Main Authors: Ajoolabady, Amir, Chiong, Mario, Lavandero, Sergio, Klionsky, Daniel J., Ren, Jun
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01.10.2022
• Subjects: cardiovascular disease; heart failure; mitophagy; mitophagy inducers; myocardial infarction; therapeutics; cardiovascular disease; heart failure; mitophagy inducers; mitophagy; therapeutics; myocardial infarction
• ISSN: 1471-4914; 1471-499X; 1471-499X
• DOI: 10.1016/j.molmed.2022.06.007

With the growing prevalence of cardiovascular disease (CVD), there is an urgent need to explore non-conventional therapeutic measures to alleviate the burden of CVD on global healthcare. Mitochondrial injury plays a cardinal role in the pathogenesis of CVD. Mitochondrial dynamics and mitophagy are essential machineries that govern mitochondrial health in cardiomyocytes in physiological and pathophysiological settings. However, with the onset and progression of CVD, homeostasis of mitophagy is disturbed through largely unknown pathological mechanisms, causing mitochondrial damage and ultimately cardiomyocyte death. In this review we decipher the dual regulatory role of mitophagy in CVD pathogenesis, summarize controversies in mitophagy, and highlight recently identified compounds capable of modulating mitophagy. We share our perspectives on future mitophagy research directions in the context of CVD. Mitophagy dysfunction underscores the pathogenesis of cardiovascular disease (CVD), leading to mitochondrial damage, reactive oxygen species (ROS) generation, and ultimately the onset or progression of various subsets of CVD.Basal induction of mitophagy preserves mitochondrial health in cardiovascular cells and thereby prevents mitochondrial damage/mitophagy dysfunction-initiated CVD.Unlike basal mitophagy, excessive/unchecked activation of mitophagy may exert negative impacts on mitochondrial health and homeostasis in cardiovascular cells, leading to maladaptive responses, apoptosis, and exacerbation of CVD.