The effect of mitochondrial-associated endoplasmic reticulum membranes (MAMs) modulation: New insights into therapeutic targets for depression

Depression is a prevalent mental disorder with high morbidity and mortality and its pathogenesis remains exactly unclarified. However, mitochondria and endoplasmic reticulum (ER) are two highly dynamic organelles that perform an indispensable role in the development of depression. Mitochondrial dysfunction and ER stress are recognized as vital pathological hallmarks in depression. The changes of intracellular activities such as mitochondrial dynamics, mitophagy, energy metabolism and ER stress are closely correlated with the progression of depression. Moreover, organelles interactions are conducive to homeostasis and cellular functions, and mitochondrial-associated endoplasmic reticulum membranes (MAMs) serve as signaling hubs of the two organelles and the coupling of the pathological progression. The main roles of MAMs are involved in metabolism, signal transduction, lipid transport, and maintenance of its structure and function. At present, accumulating studies elucidated that MAMs have gradually become a novel therapeutic target in treatment of depression. In the review, we focus on influence of mitochondria dysfunction and ER stress on depression. Furthermore, we discuss the underlying role of MAMs in depression and highlight natural products targeting MAMs as potential antidepressants to treat depression.