%0 Journal Article %J Science %D 2009 %T Genome-wide RNAi screen identifies Letm1 as a mitochondrial Ca2+/H+ antiporter. %A Jiang, Dawei %A Zhao, Linlin %A Clapham, David E %K Animals %K Antiporters %K calcium %K Calcium-Binding Proteins %K Cation Transport Proteins %K Cell Line %K drosophila melanogaster %K Drosophila Proteins %K Genome, Human %K Genome, Insect %K HeLa Cells %K Humans %K Hydrogen %K Hydrogen-Ion Concentration %K Ion Transport %K Membrane Potential, Mitochondrial %K Membrane Proteins %K mitochondria %K Mitochondrial Membranes %K Mitochondrial Proteins %K Proteolipids %K RNA Interference %X

Mitochondria are integral components of cellular calcium (Ca2+) signaling. Calcium stimulates mitochondrial adenosine 5'-triphosphate production, but can also initiate apoptosis. In turn, cytoplasmic Ca2+ concentrations are regulated by mitochondria. Although several transporter and ion-channel mechanisms have been measured in mitochondria, the molecules that govern Ca2+ movement across the inner mitochondrial membrane are unknown. We searched for genes that regulate mitochondrial Ca2+ and H+ concentrations using a genome-wide Drosophila RNA interference (RNAi) screen. The mammalian homolog of one Drosophila gene identified in the screen, Letm1, was found to specifically mediate coupled Ca2+/H+ exchange. RNAi knockdown, overexpression, and liposome reconstitution of the purified Letm1 protein demonstrate that Letm1 is a mitochondrial Ca2+/H+ antiporter.

%B Science %V 326 %P 144-7 %8 2009 Oct 2 %G eng %N 5949 %1 http://www.ncbi.nlm.nih.gov/pubmed/19797662?dopt=Abstract %R 10.1126/science.1175145