Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antiporters / genetics*
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Antiporters / metabolism
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Calcium / metabolism*
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Calcium-Binding Proteins / genetics*
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Calcium-Binding Proteins / metabolism*
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Cation Transport Proteins / genetics
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Cation Transport Proteins / metabolism
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Cell Line
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Drosophila Proteins / genetics*
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Drosophila Proteins / metabolism
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Drosophila melanogaster / genetics*
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Drosophila melanogaster / metabolism
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Genome, Human
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Genome, Insect
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HeLa Cells
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Humans
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Hydrogen / metabolism
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Hydrogen-Ion Concentration
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Ion Transport
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Membrane Potential, Mitochondrial
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Membrane Proteins / genetics*
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Membrane Proteins / metabolism*
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Mitochondria / metabolism*
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Mitochondrial Membranes / metabolism
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Mitochondrial Proteins / genetics
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Mitochondrial Proteins / metabolism*
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Proteolipids / metabolism
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RNA Interference*
Substances
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Antiporters
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Calcium-Binding Proteins
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Cation Transport Proteins
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Drosophila Proteins
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LETM1 protein, human
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Letm1 protein, Drosophila
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Membrane Proteins
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Mitochondrial Proteins
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Proteolipids
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calcium-hydrogen antiporters
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proteoliposomes
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Hydrogen
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Calcium