Fig. 1. Structure and function of the MAMs.

Close interaction between ER and mitochondria are necessary for a plethora of function. This peculiar microdomain is called mitochondrial-associated membranes (MAMs). The structure of the MAMs is tightly controlled by the interaction of MFN2/MFN1/2, FIS1/BAP31, PTPIP51/VAPB, and EMERIN-FATE1-MITOFILIN. The truncated form of SERCA1, S1T, PDZD8, TpM, and PERK may also participate in MAM tethering. MITOL and PACS2 influence MAM's structure by interacting with MFN2 and BAP31, respectively. The apposition of ER to mitochondria allows the passage of Ca²⁺ from the ER lumen to the mitochondria through the tripartite complex, IP3R (the ER IP3-sensitive Ca²⁺ channel), GRP75 (a cytoplasmic chaperone), and VDAC (the OMM Ca²⁺ channel). This transfer may be modulated by S1R, BiP, calnexin, and PML, for instance. The entrance of Ca²⁺ into the mitochondrial matrix occurs via MCU (the mitochondrial calcium uniporter). The Ca²⁺ is necessary for the correct function of the TCA cycle and for the respiratory complexes. Some proteins involved in neurodegenerative diseases are expressed in MAMs, such as HTT, α-synuclein, APOE4, and PS1-2