Mitochondria-ER contact sites in neurological disorders

Mitochondria-associated ER membranes (MAMs) are inter-organelle contact sites that mediate signaling between the ER and mitochondria. MAMs play crucial roles in Ca2+ transfer, lipid metabolism, mitochondrial respiration, protein homeostasis, autophagy, and ER stress. In the central nervous system (CNS), these functions are particularly important because neurons and glial cells require precise communication between ER and mitochondria to sustain various neuronal functions. Previous studies often interpreted the MAM dysfunction associated with disease as an alteration in ER-mitochondria coupling. More recently, however, MAMs are regarded as functionally specialized signaling platforms whose molecular composition is dynamic, cell type- and disease stage-dependent. Here, we discuss how MAM remodeling underlies a range of neurological diseases, including neurodegenerative and neurodevelopmental conditions, neuropsychiatric disorders, neuroinflammation, neuronal aging, and brain tumors.