Mitochondrial Ca2+ homeostasis: mechanism, role, and tissue specificities

Mitochondria from every tissue are quite similar in their capability to accumulate Ca(2+) in a process that depends on the electrical potential across the inner membrane; it is catalyzed by a gated channel (named mitochondrial Ca(2+) uniporter), the molecular identity of which has only recently been unraveled. The release of accumulated Ca(2+) in mitochondria from different tissues is, on the contrary, quite variable, both in terms of speed and mechanism: a Na(+)-dependent efflux in excitable cells (catalyzed by NCLX) and a H(+)/Ca(2+) exchanger in other cells. The efficacy of mitochondrial Ca(2+) uptake in living cells is strictly dependent on the topological arrangement of the organelles with respect to the source of Ca(2+) flowing into the cytoplasm, i.e., plasma membrane or intracellular channels. In turn, the structural and functional relationships between mitochondria and other cellular membranes are dictated by the specific architecture of different cells. Mitochondria not only modulate the amplitude and the kinetics of local and bulk cytoplasmic Ca(2+) changes but also depend on the Ca(2+) signal for their own functionality, in particular for their capacity to produce ATP. In this review, we summarize the processes involved in mitochondrial Ca(2+) handling and its integration in cell physiology, highlighting the main common characteristics as well as key differences, in different tissues.