The gatekeepers of mitochondrial calcium influx: MICU1 and MICU2.

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