The renaissance of mitochondrial calcium transport

Although the capacity of mitochondria for accumulating Ca2+ down the electr ical gradient generated by the respiratory chain has been known for over th ree 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 Ca2+ transporters would allow significant uptake only in conditions of cellular Ca2+ overload. Conversely, the direct measuremen t of [Ca2+] in the mitochondrial matrix revealed major [Ca2+] increases upo n agonist stimulation. In this review, we will summarize: (a) the mechanism s that allow this large response, reconciling the biochemical properties of the transporters and the large amplitude of the mitochondrial [Ca2+] rises , and (b) the biological role of mitochondrial Ca2+ signalling, that encomp asses the regulation of mitochondrial function and the modulation of the sp atio-temporal pattern of cytosolic [Ca2+] increases.