Potential role of mitochondria-associated endoplasmic reticulum membrane proteins in diseases

Mitochondria-associated endoplasmic reticulum membranes (MAMs) are dynamic membrane coupling regions formed by the coupling of the mitochondrial outer membrane and endoplasmic reticulum (ER). MAMs are involved in the mitochondrial dynamics, mitophagy, Ca2+ exchange, and ER stress. A large number of studies indicate that many proteins are involved in the formation of MAMs, including dynamic-related protein 1 (Drp1), DJ-1, PTEN-induced putative kinase 1 (PINK), α-synuclein (α-syn), sigma-1 receptor (S1R), mitofusin-2 (Mfn2), presenilin-1 (PS1), protein kinase R (PKR)-like ER kinase (PERK), Parkin, Cyclophilin D (CypD), glucose-related protein 75 (Grp75), FUN14 domain containing 1 (Fundc1), vesicle-associated membrane-protein-associated protein B (VAPB), phosphofurin acidic cluster sorting protein 2 (PACS-2), ER oxidoreductin 1 (Ero1), and receptor expression-enhancing protein 1 (REEP1). These proteins play an important role in the structure and functions of the MAMs. Abnormalities in these MAM proteins further contribute to the occurrence and development of related diseases, such as neurodegenerative diseases, non-alcoholicfattyliverdisease (NALFD), type 2 diabetes mellitus (T2DM), and diabetic kidney (DN). In this review, we introduce important proteins involved in the structure and the functions of the MAMs. Furthermore, we effectively summarize major insights about these proteins that are involved in the physiopathology of several diseases through the effect on MAMs.