Store-Operated Ca²⁺ Entry (SOCE) Pathways

András Spät, Gergö Szanda

Mitochondria extensively modify virtually all cellular Ca(2+) transport processes, and store-operated Ca(2+) entry (SOCE) is no exception to this rule. The interaction between SOCE and mitochondria is complex and reciprocal, substantially altering and, ultimately, fine-tuning both capacitative Ca(2+) influx and mitochondrial function. Mitochondria, owing to their considerable Ca(2+) accumulation ability, extensively buffer the cytosolic Ca(2+) in their vicinity. In turn, the accumulated ion is released back into the neighboring cytosol during net Ca(2+) efflux. Since store depletion itself and the successive SOCE are both Ca(2+)-regulated phenomena, mitochondrial Ca(2+) handling may have wide-ranging effects on capacitative Ca(2+) influx at any given time. In addition, mitochondria may also produce or consume soluble factors known to affect store-operated channels. On the other hand, Ca(2+) entering the cell during SOCE is sensed by mitochondria, and the ensuing mitochondrial Ca(2+) uptake boosts mitochondrial energy metabolism and, if Ca(2+) overload occurs, may even lead to apoptosis or cell death. In several cell types, mitochondria seem to be sterically excluded from the confined space that forms between the plasma membrane (PM) and endoplasmic reticulum (ER) during SOCE. This implies that high-Ca(2+) microdomains comparable to those observed between the ER and mitochondria do not form here. In the following chapter, the above aspects of the many-sided SOCE-mitochondrion interplay will be discussed in greater detail.