Targeting mitophagy in the heart: Exploring the therapeutic potential of MicroRNAs

Abstract

Mitophagy, a selective form of autophagy, plays an indispensable role in preserving mitochondrial integrity by eliminating dysfunctional mitochondria, thereby sustaining cellular homeostasis. This process is particularly critical in cardiomyocytes, which rely heavily on high-quality mitochondria to meet their substantial energy demands. Impaired mitophagy has been implicated in the pathogenesis of various cardiovascular diseases, including ischemic heart disease, heart failure, and cardiomyopathy. Emerging evidence highlights the pivotal regulatory role of microRNAs (miRNAs)—small non-coding RNA molecules—in modulating mitophagy by targeting key genes such as PINK1, Parkin, and FUNDC1, which are integral to mitochondrial quality control. This review comprehensively examines the dual capacity of miRNAs to either enhance or suppress mitophagy and evaluates the implications of these regulatory actions for cardiovascular health. For instance, miRNAs such as miR-24–3p and miR-125a-5p modulate mitophagy pathways, influencing cardiac function in distinct ways. Additionally, miRNAs like miR-34a and miR-330–3p may exert broader effects on mitochondrial homeostasis in cardiac tissue. This paper further explores the therapeutic potential of targeting miRNAs to restore mitophagy equilibrium and mitigate mitochondrial dysfunction, offering novel avenues for cardiovascular disease management. By synthesizing recent findings, this review underscores the promise of miRNA-based interventions and identifies critical directions for future research.