FIGURE 7.

Spatial segregation of mitochondrial Ca²⁺ influx and efflux pathways in cardiomyocytes. In cardiac muscle, the mitochondrial calcium uniporter complex (mtCU) is found at regions of the inner mitochondrial membrane (IMM) near contacts between the outer mitochondrial membrane and Ca²⁺ release sites on the sarcoplasmic reticulum (SR). This arrangement enables Ca²⁺ released from the SR via the ryanodine receptor (RyR2) to be taken up efficiently into the mitochondrial matrix. NCLX, the principal route for mitochondrial Ca²⁺ efflux in cardiomyocytes, is instead distributed at regions of the IMM that are more distant from the sites of SR-mitochondria contact. This spatial separation of mitochondrial Ca²⁺ uptake and efflux is thought to minimize futile cycling of Ca²⁺ flux through the mtCU and NCLX that would otherwise depolarize mitochondrial membrane potential. See glossary for abbreviations.