Date: 22 Dec 2011

Mitochondrial Ca2+ as a Key Regulator of Mitochondrial Activities

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Mitochondria play a central role in cell biology, not only as producers of ATP but also as regulators of the Ca2+ 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 Ca2+ through an electrogenic pathway, the uniporter, that acts to equilibrate Ca2+ 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 Ca2+ affinity, demands high local Ca2+ concentrations to work. In different cell systems these high Ca2+ concentration microdomains are generated, upon cell stimulation, in proximity of the plasma membrane and the sarco/endoplasmic reticulum Ca2+ channels.

Recent work has revealed the central role of mitochondria in signal transduction pathways: evidence is accumulating that, by taking up Ca2+, they not only modulate mitochondrial activities but also tune the cytosolic Ca2+ signals and their related functions. This review analyses recent developments in the area of mitochondrial Ca2+ signalling and attempts to summarize cell physiology aspects of the mitochondrial Ca2+ transport machinery.