The mitochondrial calcium uniporter is a highly selective ion channel

During intracellular Ca2+ signalling mitochondria accumulate significant amounts of Ca2+ from the cytosol(1,2). Mitochondrial Ca2+ uptake controls the rate of energy production(1,3,4), shapes the amplitude and spatio- temporal patterns of intracellular Ca2+ signals(1,5-8), and is instrumental to cell death(9,10). This Ca2+ uptake is undertaken by the mitochondrial Ca2+ uniporter ( MCU) located in the organelle's inner membrane(11,12). The uniporter passes Ca2+ down the electrochemical gradient maintained across this membrane without direct coupling to ATP hydrolysis or transport of other ions(11). Carriers are characterized by turnover numbers that are typically 1,000- fold lower than ion channels, and until now it has been unclear whether the MCU is a carrier or a channel(13). By patch- clamping the inner mitochondrial membrane, we identified a previously unknown Ca2+ selective ion channel sensitive to inhibitors of mitochondrial Ca2+ uptake. Our data indicate that this unique channel binds Ca2+ with extremely high affinity ( dissociation constant less than or equal to 2 nM), enabling high Ca2+ selectivity despite relatively low cytoplasmic Ca2+ concentrations. The channel is inwardly rectifying, making it especially effective for Ca2+ uptake into energized mitochondria. Thus, we conclude that the properties of the current mediated by this novel channel are those of the MCU.