Mitophagy as a therapeutic target for myocardial fibrosis: Mechanistic insights and potential pharmacological interventions

Myocardial fibrosis is a central pathological feature of various cardiovascular diseases, including heart failure and hypertension. It involves the activation of cardiac fibroblasts, transforming them into myofibroblasts that secrete pro-fibrotic factors, leading to excessive extracellular matrix deposition and progressive cardiac dysfunction. Mitochondrial dysfunction plays a critical role in the development of myocardial fibrosis, with mitophagy, a selective form of autophagy, essential for maintaining mitochondrial quality by removing damaged mitochondria. This process is vital in mitigating fibrosis progression. Recent studies suggest that pharmacological modulation of mitophagy may offer novel therapeutic strategies for cardiovascular diseases involving fibrosis. This review explores the mechanisms of mitophagy in myocardial fibrosis, highlighting key proteins and molecular pathways involved in fibroblast activation and mitochondrial dysfunction. Additionally, it discusses the therapeutic potential of targeting mitophagy to mitigate myocardial fibrosis, emphasizing the importance of balancing mitophagy modulation. Overall, targeting mitophagy pathways holds promise as a therapeutic approach for managing myocardial fibrosis and improving heart function.