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

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 patholog-ical 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 perspec-tives on future mitophagy research directions in the context of CVD.

Automated summary

With the increasing prevalence of cardiovascular disease (CVD), it is crucial to explore unconventional therapeutic measures to alleviate the burden of CVD on global healthcare. Mitochondrial injury is a key factor in the development of CVD, and mitochondrial dynamics and mitophagy play important roles in regulating mitochondrial health in cardiomyocytes. However, the progression of CVD disturbs the homeostasis of mitophagy through unknown pathological mechanisms, resulting in mitochondrial damage and cardiomyocyte death. In this review, the dual regulatory role of mitophagy in CVD pathogenesis is discussed, controversies in mitophagy are summarized, and recently identified compounds capable of modulating mitophagy are highlighted. The future research directions of mitophagy in the context of CVD are also shared.