Fig. 2.

Schematic representation of intracellular Ca²⁺ dynamics. a Ca²⁺ entry and exit are regulated by SOC and PMCA channels, respectively, on the plasma membrane. Ca²⁺ is transported into the ER lumen by SERCA and released through IP₃R. Type 1 IP₃Rs (IP₃R1) mediate cytosolic Ca²⁺ efflux and type 3 IP₃Rs (IP₃R3) mediate mitochondrial Ca²⁺ efflux. b IP₃R3s enriched at MAM are found in a complex with Sig-1R and BiP, and are additionally linked to VDAC on the OMM by grp75. VDAC tightly controls Ca²⁺ permeation by IP₃R3-mediated Ca²⁺ signals. Once Ca²⁺ transverses the OMM, Ca²⁺ uniporters transmit Ca²⁺ into the mitochondrial matrix