The gatekeepers of mitochondrial calcium influx: MICU 1 and MICU 2

The receptor‐evoked C a 2+ signal is sensed and translated by mitochondria. Physiological cytoplasmic C a 2+ ([ C a 2+ ] c ) oscillations result in mitochondrial C a 2+ ([ C a 2+ ] m ) oscillations, while large and sustained [ C a 2+ ] c increase results in a pathologic increase in basal [ C a 2+ ] m and in C a 2+ accumulation. The physiological [ C a 2+ ] m signal regulates [ C a 2+ ] c and stimulates oxidative metabolism, while excess C a 2+ accumulation causes cell stress leading to cell death. [Ca 2+ ] m is determined by Ca 2+ uptake mediated by the mitochondria C a 2+ uniporter ( MCU ) channel and by Na + ‐ and H + ‐coupled C a 2+ extrusion [1][Drago I, 2011].