Plastic mitochondria-endoplasmic reticulum (ER) contacts use chaperones and tethers to mould their structure and signaling

Mitochondria-endoplasmic reticulum (ER) contacts (MERCs), biochemically isolated as the mitochondria-associated membrane (MAM), were discovered on electron micrographs in the early 1950s. Since the 1990s, we know that the two organelles exchange lipids and Ca2+ ions at these membrane contacts. Already in the very first publication on this intracellular structure, the extreme plasticity of the structure was obvious. Recent progress has now confirmed that ER and mitochondria move closer to deepen physical contacts under conditions of ER stress, hypoxia, or short-term nutrient deprivation, while nutrient over-supply is one situation that lessens contacts. Signaling associated with these intracellular events moulds the contact site ultrastructure, in particular during autophagy, apoptosis and alterations of mitochondria metabolism. Tethering complexes, as well as key MAM proteins including chaperones of the ER and mitochondriacontrol the plasticity of MERC structures. It has become evident that altered MAM composition and changes in MAM plasticity are critical factors for the development of cancer, neurodegeneration and the metabolic syndrome.