IP3 receptors (IP3Rs) in the ER membrane release local accumulations of cytosolic Ca2+, which are taken up by mitochondria through the voltage-dependent anion channel (VDAC) in the outer mitochondrial membrane. Then, Ca2+ ions are transported into the mitochondrial matrix by the mitochondrial calcium uniporter (MCU). This arrangement allows Ca2+ signaling between the ER and mitochondria at membrane contact sites without globally increasing cytosolic Ca2+ levels.
