Mitophagy in cardiovascular disease: From mechanistic insights to therapeutic horizons.

Cardiovascular diseases (CVDs) remain a leading cause of death worldwide, with a complex and multifactorial pathophysiology. Given its high energy demands, the heart is critically dependent on mitochondrial energy production and metabolic homeostasis. Mitophagy, a selective form of autophagy, represents a crucial intracellular mechanism for preserving cardiac cellular function. This review summarizes the roles of mitophagy in various cardiovascular pathologies, including cardiac aging, myocardial hypertrophy, heart failure, myocardial infarction, ischemia-reperfusion injury. Evidence indicates that mitophagy is mediated through both Parkin-dependent and -independent pathways. Moreover, several natural compounds and small-molecule agents have demonstrated potential in attenuating myocardial injury and improving cardiac function by modulating mitophagy-related signaling. Despite significant advances in understanding mitophagy's role in CVDs, the precise molecular mechanisms and regulatory networks across different pathological contexts require further elucidation. Future research should focus on deciphering the complex regulatory landscape of mitophagy, developing targeted therapies, and advancing their clinical translation and safety evaluation.