Mitochondria-associated endoplasmic reticulum membranes and myocardial ischemia: from molecular mechanisms to therapeutic strategies

Myocardial ischemia has the highest disease burden among all cardiovascular diseases making it a significant challenge to the global public health. It can result in myocardial cell damage and death due to impaired mitochondrial and endoplasmic reticulum (ER) functions. These two organelles are important regulators of cell death. In recent years, research has shifted from isolated studies of individual organelles to a more integrative approach, with a particular focus on their membrane contact sites-Mitochondria-Associated Endoplasmic Reticulum Membranes (MAMs). These dynamic microdomains play a crucial role in regulating material exchange and signal transduction between the endoplasmic reticulum and mitochondria. This review comprehensively describes the intricate structure of MAMs and their multifaceted roles in cellular pathophysiological processes. Particular focus was directed at the far-reaching effects of MAMs in regulating key pathological events including calcium homeostasis, mitochondrial dysfunction, ER stress, oxidative stress, and autophagy in ischemic heart disease (IHD). The potential treatment targets and regulatory mechanisms of MAMs were discussed and summarized, providing novel research directions and treatment approaches for improving myocardial ischemia-related diseases.