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PMID:19797662

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Citation

Jiang, D, Zhao, L and Clapham, DE (2009) Genome-wide RNAi screen identifies Letm1 as a mitochondrial Ca2+/H+ antiporter. Science 326:144-7

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.

Links

PubMed Online version:10.1126/science.1175145

Keywords

Animals; Antiporters/genetics; Antiporters/metabolism; Calcium/metabolism; Calcium-Binding Proteins/genetics; Calcium-Binding Proteins/metabolism; Cation Transport Proteins/genetics; Cation Transport Proteins/metabolism; Cell Line; Drosophila Proteins/genetics; Drosophila Proteins/metabolism; Drosophila melanogaster/genetics; Drosophila melanogaster/metabolism; Genome, Human; Genome, Insect; HeLa Cells; Humans; Hydrogen/metabolism; Hydrogen-Ion Concentration; Ion Transport; Membrane Potential, Mitochondrial; Membrane Proteins/genetics; Membrane Proteins/metabolism; Mitochondria/metabolism; Mitochondrial Membranes/metabolism; Mitochondrial Proteins/genetics; Mitochondrial Proteins/metabolism; Proteolipids/metabolism; RNA Interference

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

LEIMA:E9ADU9

enables

GO:0005432: calcium:sodium antiporter activity

ECO:0000266: sequence orthology evidence used in manual assertion

GeneDB:TcCLB.507951.270

F

Seeded From UniProt

complete

LEIMA:E9ADU9

located_in

GO:0016021: integral component of membrane

ECO:0000266: sequence orthology evidence used in manual assertion

GeneDB:TcCLB.507951.270

C

Seeded From UniProt

complete

LEIMA:E9ADU9

located_in

GO:0005743: mitochondrial inner membrane

ECO:0000266: sequence orthology evidence used in manual assertion

GeneDB:TcCLB.507951.270

C

Seeded From UniProt

complete

HUMAN:LETM1

involved_in

GO:0099093: calcium export from the mitochondrion

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:LETM1

enables

GO:0015369: calcium:proton antiporter activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:LETM1

involved_in

GO:0051560: mitochondrial calcium ion homeostasis

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:LETM1

located_in

GO:0005743: mitochondrial inner membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:LETM1

involved_in

GO:0006851: mitochondrial calcium ion transmembrane transport

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:LETM1

enables

GO:0005432: calcium:sodium antiporter activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

DROME:LETM1

located_in

GO:0031966: mitochondrial membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DROME:LETM1

involved_in

GO:0006851: mitochondrial calcium ion transmembrane transport

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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Backtrace:

#0 /usr/local/github/wiki-extensions/wiki-extensions-hulab/AnnotationLinks/AnnotationLinks.php(70): AnnotationLinks::getQuickGOannotations(string, array)
#1 /var/www/html/go/wiki/includes/parser/Parser.php(3888): AnnotationLinks::renderAnnotations(NULL, array, Parser, PPFrame_DOM)
#2 /var/www/html/go/wiki/includes/parser/Preprocessor_DOM.php(1362): Parser->extensionSubstitution(array, PPFrame_DOM)
#3 /var/www/html/go/wiki/includes/parser/Parser.php(2942): PPFrame_DOM->expand(DOMElement, integer)
#4 /var/www/html/go/wiki/includes/parser/Parser.php(1293): Parser->replaceVariables(string)
#5 /var/www/html/go/wiki/includes/parser/Parser.php(443): Parser->internalParse(string)
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#8 /var/www/html/go/wiki/includes/content/ContentHandler.php(1324): AbstractContent->getParserOutput(Title, integer, ParserOptions)
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#10 /usr/local/github/wiki-extensions/wiki-extensions-hulab/CirrusSearch/includes/Updater.php(407): CirrusSearch\Updater::buildDocument(CirrusSearch, WikiPage, CirrusSearch\Connection, integer, integer, integer)
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#12 /usr/local/github/wiki-extensions/wiki-extensions-hulab/CirrusSearch/includes/Updater.php(83): CirrusSearch\Updater->updatePages(array, integer)
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#14 /usr/local/github/wiki-extensions/wiki-extensions-hulab/CirrusSearch/includes/Job/Job.php(99): CirrusSearch\Job\LinksUpdate->doJob()
#15 /var/www/html/go/wiki/includes/jobqueue/JobRunner.php(296): CirrusSearch\Job\Job->run()
#16 /var/www/html/go/wiki/includes/jobqueue/JobRunner.php(193): JobRunner->executeJob(CirrusSearch\Job\LinksUpdate, Wikimedia\Rdbms\LBFactorySimple, BufferingStatsdDataFactory, integer)
#17 /var/www/html/go/wiki/includes/MediaWiki.php(1002): JobRunner->run(array)
#18 /var/www/html/go/wiki/includes/MediaWiki.php(988): MediaWiki->triggerSyncJobs(integer, MediaWiki\Logger\LegacyLogger)
#19 /var/www/html/go/wiki/includes/MediaWiki.php(912): MediaWiki->triggerJobs()
#20 /var/www/html/go/wiki/includes/MediaWiki.php(727): MediaWiki->restInPeace(string, boolean)
#21 /var/www/html/go/wiki/includes/MediaWiki.php(750): MediaWiki->{closure}()
#22 /var/www/html/go/wiki/includes/MediaWiki.php(557): MediaWiki->doPostOutputShutdown(string)
#23 /var/www/html/go/wiki/index.php(42): MediaWiki->run()
#24 {main}

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