The mitochondrial associated endoplasmic reticulum membranes: A platform for the pathogenesis of inflammation-mediated metabolic diseases

Abstract

Mitochondria-associated endoplasmic reticulum membranes (MAM) are specialized subcellular compartments that are shaped by endoplasmic reticulum (ER) subdomains placed side by side to the outer membrane of mitochondria (OMM) being connected by tethering proteins in mammalian cells. Studies showed that MAM has multiple physiological functions. These include regulation of lipid synthesis and transport, Ca2+ transport and signaling, mitochondrial dynamics, apoptosis, autophagy, and formation and activation of an inflammasome. However, alterations of MAM integrity lead to deleterious effects due to an increased generation of mitochondrial reactive oxygen species (ROS) via increased Ca2+ transfer from the ER to mitochondria. This, in turn, causes mitochondrial damage and release of mitochondrial components into the cytosol as damage-associated molecular patterns which rapidly activate MAM-resident Nod-like receptor protein-3 (NLRP3) inflammasome components. This complex induces the release of pro-inflammatory cytokines that initiate low-grade chronic inflammation that subsequently causes the development of metabolic diseases. But, the mechanisms of how MAM is involved in the pathogenesis of these diseases are not exhaustively reviewed. Therefore, this review was aimed to highlight the contribution of MAM to a variety of cellular functions and consider its significance pertaining to the pathogenesis of inflammation-mediated metabolic diseases.