Mitochondria-Associated Endoplasmic Reticulum Membranes in Health and Diseases

Membrane contact sites enable organelles to interact closely, thereby coordinating cellular homeostasis and functional regulation. Among diverse subcellular membrane architectures, mitochondria-associated endoplasmic reticulum membranes (MAMs) assume a crucial role in the physiological and pathological environments. A plethora of cellular processes are intertwined with MAMs, such as Ca²⁺ translocation, lipid metabolism, endoplasmic reticulum (ER) stress response, mitochondrial dynamics, and mitophagy. In the event of improper modulation of MAMs components, the incidence of diseases would surge remarkably. This review endeavors to expound upon the functions of key MAMs proteins in healthy state and decipher their regulatory mechanisms under physiological and pathological circumstances. In addition, we try to probe into the specific contribution of MAMs within the occurrence and development of diseases, and subsequently collate drug compounds and clinical trials that target MAMs components. Finally, we proffer our insights regarding the contentious perspectives and prospective research directions of MAMs. Understanding the roles and mechanisms of MAMs may potentially offer novel diagnostic biomarkers and treatment targets in clinical practice, paving the way for more precise and effective clinical interventions for common diseases.