TY - JOUR T1 - Genome-wide RNAi screen identifies Letm1 as a mitochondrial Ca2+/H+ antiporter. JF - Science Y1 - 2009 A1 - Jiang, Dawei A1 - Zhao, Linlin A1 - Clapham, David E KW - Animals KW - Antiporters KW - calcium KW - Calcium-Binding Proteins KW - Cation Transport Proteins KW - Cell Line KW - drosophila melanogaster KW - Drosophila Proteins KW - Genome, Human KW - Genome, Insect KW - HeLa Cells KW - Humans KW - Hydrogen KW - Hydrogen-Ion Concentration KW - Ion Transport KW - Membrane Potential, Mitochondrial KW - Membrane Proteins KW - mitochondria KW - Mitochondrial Membranes KW - Mitochondrial Proteins KW - Proteolipids KW - RNA Interference AB -

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.

VL - 326 IS - 5949 U1 - http://www.ncbi.nlm.nih.gov/pubmed/19797662?dopt=Abstract ER -