Mitochondrial-organelle communication in ischemic heart disease: mechanisms, pathological implications, and therapeutic opportunities

Ischemic heart disease (IHD) remains the predominant cause of cardiovascular mortality globally, with mitochondrial dysfunction serving as a central pathological driver. Mitochondria not only function as the core hub for energy metabolism in cardiomyocytes but also establish extensive physical interactions with the endoplasmic reticulum, lysosomes, lipid droplets, and peroxisomes through membrane contact sites (MCSs). These inter-organelle contacts collaboratively regulate calcium homeostasis, lipid metabolism, mitochondrial quality control, and energy metabolism, thereby forming a mitochondria-centered organelle communication network. Impairment of mitochondrial‑organelle communication critically contributes to the onset and development of IHD. Given the pivotal role of mitochondrial-organelle communication in IHD pathogenesis, this network has emerged as an attractive therapeutic target. Strategies including small-molecule or peptide modulators, gene therapy, targeted nanoparticle delivery, and mitochondrial transplantation offer significant potential to alleviate myocardial injury by regulating mitochondrial-organelle MCSs. This review aims to deepen the mechanistic understanding of mitochondrial-organelle communication, provide novel insights into current IHD treatment strategies, and establish a theoretical foundation for the development of novel targeted interventions.