Mitochondrial Ca 2+ as a key regulator of mitochondrial activities

Abstract

Mitochondria play a central role in cell biology, not only as producers of ATP but also as regulators of the Ca 2+ signal. The translocation by respiratory chain protein complexes of H + across the ion-impermeable inner membrane generates a very large H + electrochemical gradient that can be employed not only by the H + ATPase to run the endoergonic reaction of ADP phosphorylation, but also to accumulate cations into the matrix. Mitochondria can rapidly take up Ca 2+ through an electrogenic pathway, the uniporter, that acts to equilibrate Ca 2+ with its electrochemical gradient, and thus accumulates the cation into the matrix, and they can release it through two exchangers (with H + and Na +, mostly expressed in non-excitable and excitable cells, respectively), that utilize the electrochemical gradient of the monovalent cations to prevent the attainment of electrical equilibrium. The uniporter, due to its low Ca 2+ affinity, demands high local Ca 2+ concentrations to work. In different cell systems these high Ca 2+ concentration microdomains are generated, upon cell stimulation, in proximity of the plasma membrane and the sarco/endoplasmic reticulum Ca 2+ channels. Recent work has revealed the central role of mitochondria in signal transduction pathways: evidence is accumulating that, by taking up Ca 2+, they not only modulate mitochondrial activities but also tune the cytosolic Ca 2+ signals and their related functions. This review analyses recent developments in the area of mitochondrial Ca 2+ signalling and attempts to summarize cell physiology aspects of the mitochondrial Ca 2+ transport machinery. © 2012 Springer Science+Business Media B.V.