Abstract 091: Mitochondrial Calcium Currents Are Conducted By A Pore Encoded By The MCU Gene.
Mitochondrial uptake of calcium (Ca 2+ ) in cardiomyocytes is thought to regulate cell survival and match ATP production to energetic demands. Of multiple pathways allowing such entry, the mitochondrial Ca 2+ uniporter is a highly Ca 2+ -selective channel encoded by several recently-discovered genes. However, which of these several genes encodes the pore-forming subunit of the channel remains an open question. Using whole-mitoplast voltage-clamping, we show that RNAi-mediated knockdown of the mitochondrial calcium uniporter ( MCU ) gene reduces the uniporter current ( I MiCa ), whereas overexpression increases it. Mutations in the putative pore domain alter key features of I MiCa , such as its strong affinity for ruthenium red, a classic uniporter blocker. These analyses demonstrate that MCU encodes the pore-forming subunit of the uniporter channel.