The renaissance of mitochondrial calcium transport

Although the capacity of mitochondria for accumulating Ca(2+) down the electrical gradient generated by the respiratory chain has been known for over three decades, the physiological significance of this phenomenon has been re-evaluated only recently. Indeed, it was long believed that the low affinity of the mitochondrial Ca(2+) transporters would allow significant uptake only in conditions of cellular Ca(2+) overload. Conversely, the direct measurement of [Ca(2+)] in the mitochondrial matrix revealed major [Ca(2+)] increases upon agonist stimulation. In this review, we will summarize: (a) the mechanisms that allow this large response, reconciling the biochemical properties of the transporters and the large amplitude of the mitochondrial [Ca(2+)] rises, and (b) the biological role of mitochondrial Ca(2+) signalling, that encompasses the regulation of mitochondrial function and the modulation of the spatio-temporal pattern of cytosolic [Ca(2+)] increases.