Mitochondrial Ca²⁺ signaling

Mitochondrial Ca²⁺ regulation is crucial for bioenergetics and cellular signaling. The mechanisms controlling mitochondrial calcium homeostasis have been recently unraveled with the discovery of mitochondrial inner membrane proteins that regulate mitochondrial Ca²⁺ uptake and extrusion. Mitochondrial Ca²⁺ uptake depends on a large complex of proteins centered around the Ca²⁺ channel protein, mitochondrial Ca²⁺ uniporter (MCU) in close interactions with several regulatory subunits (MCUb, EMRE, MICU1, MICU2). Mitochondrial Ca²⁺ extrusion is mainly mediated by the mitochondrial Na⁺/Ca²⁺/Li⁺ exchanger (NCLX). Here, we review the major players of mitochondrial Ca²⁺ homeostasis and their physiological functions.