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Genome-Wide RNAi Screen Identifies Letm1 as a Mitochondrial Ca 2+ /H + Antiporter

Year: 2009

Type: article

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.

Source: Science

DOI: 10.1126/science.1175145

Authors: Dawei Jiang, Linlin Zhao, David E. Clapham

Institutions: Boston Children's Hospital, Howard Hughes Medical Institute, Harvard University, Manton Center for Orphan Disease Research

Language: English

Topic: Mitochondrial Function and Pathology

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: green

Funder: Howard Hughes Medical Institute

OpenAlex ID: W2002791298

FWCI: 12.87

Cites: 23

Cited by: 536

Related to: 9