New insights into the role of mitochondria-associated endoplasmic reticulum membrane

The mitochondria-associated endoplasmic reticulum membrane (MAM) is a specialized subdomain of the endoplasmic reticulum (ER) membrane that regulates ER-mitochondria communications. The MAM is characterized by direct apposition to a mitochondrion, a unique lipid profile, and the expression of a unique set of proteins involved in Ca(2+) signaling, phospholipid biosynthesis, protein folding, and membrane tethering. The association of the MAM with a mitochondrion is in part cytoskeleton independent and dynamically changed by an elevation of the cytosolic Ca(2+) level. The mechanisms underlying the genesis of MAM are unclear but might involve COPI-dependent vesicular transport and soluble NSF attachment protein receptor. The MAM is recognized as a center for intermembrane transport of phospholipids and for direct Ca(2+) transmission to mitochondria that activates the tricarboxylic acid cycle. However, MAM might be also involved in the interorganelle transport of cholesterol, ceramides, ATP, and proteins as well as in proteasomal protein degradation and lipid droplet formation. Recent studies have begun to unveil the importance of interorganelle communication in the innate immune response to virus infection and in the pathophysiology of neurodegenerative/neurodevelopmental disorders. Thus, drug discovery aimed at regulating ER-to-mitochondria communication may open a new avenue in treatments of human diseases.