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

Abstract Cytosolic calcium ( c Ca 2+ ) entry into mitochondria is facilitated by the mitochondrial membrane potential (ΔΨm), 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 ΔΨm, the mitochondrial Ca 2+ ( m Ca 2+ ) homeostasis remains normal. We show that knockdown of NDUFAF3 and SDHB reduce ETC activity altering m Ca 2+ efflux and influx rates while ΔΨm remains intact. Shifting the equilibrium toward lower [Ca 2+ ] m accumulation renders cells resistant to death. Our findings reveal an unexpected relationship between complex I and II with the m Ca 2+ homeostasis independent of ΔΨm.