FIGURE 1.

MERCs participate throughout the cell life cycle. (A) MERCs are sites of close apposition between ER and mitochondria, maintained by proteins such as Vesicle-associated membrane protein-associated protein B (VAPB) and Protein tyrosine phosphatase-interacting protein 51 (PTPIP51), which form a bridge between the surfaces of both organelles. GRP75, on the other hand, tethers the IP₃R and VDAC Ca²⁺ channels to allow for an efficient Ca²⁺ transfer. Mitofusins (MFNs) are present at the surface of both ER and mitochondria, purportedly forming a tether between both; however, this is a matter of controversy, as they have been proposed to also antagonize ER-mitochondria interaction. PACS-2, instead, is an ER-resident sorting protein enriched in MERCs, which governs MERCs composition. (B) MERCs have different functions according to the cell’s requirements. They participate in cell division, differentiation, death, survival and senescence via regulation of mitochondrial dynamics, Ca²⁺ homeostasis or ROS production.