Complex I and II are required for normal mitochondrial Ca2+ homeostasis

Cytosolic calcium (Ca-c(2+)) entry into mitochondria is facilitated by the mitochondrial membrane potential (Delta Psi m), an electrochemical gradient generated by the electron transport chain (ETC). Is has been assumed that as long as mutations that affect the ETC do not affect the Delta Psi m, the mitochondrial Ca2+ (Ca-m(2+)) homeostasis remains normal. We show that knockdown of NDUFAF3 and SDHB reduce ETC activity altering Ca-m(2+) efflux and influx rates while Delta Psi m remains intact. Shifting the equilibrium toward lower [Ca2+](m) accumulation renders cells resistant to death. Our findings reveal an unexpected relationship between complex I and II with the Ca-m(2+) homeostasis independent of Delta Psi m.