The role of mitochondria in the activation/maintenance of SOCE store-operated Ca2+ entry and mitochondria

Abstract

Mitochondria modify cellular Ca2+ transport processes and, in turn, almost every Ca2+ signaling event has a notable effect on mitochondrial function. This kind of reciprocal interplay between Ca2+ handling and mitochondria is especially prominent during store-operated Ca2+ entry (SOCE). Localization of mitochondria, Ca2+ uptake and efflux into and out of the organelle, and even release of metabolites from the mitochondria have been shown to substantially modify SOCE. On the other hand, Ca2+ entering the cell through store-operated channels is sequestered by mitochondria. The ensuing mitochondrial Ca2+ signal activates the reduction of pyridine nucleotides and promotes ATP synthesis and thereby adjusts energy metabolism to cellular demands. Mitochondrial Ca2+ accumulation also supports cell specific functions such as steroid and insulin secretion. Early observations have suggested that mitochondria need to be localized in the vicinity of store-operated channels for efficient SOCE to occur. Recent studies in numerous cell types, however, have shown that mitochondria are not located in the molecular proximity of store-operated channels but Ca2+diffuses to mitochondria from the nearby orifice of the channels. Consequently, the formation of high Ca2+ perimitochondrial microdomains is not a sine qua non for SOCE-mitochondrion cooperation.