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SLC25A51 is a mammalian mitochondrial NAD+ transporter

Mitochondria require nicotinamide adenine dinucleotide (NAD+) to carry out the fundamental processes that fuel respiration and mediate cellular energy transduction. Mitochondrial NAD+ transporters have been identified in yeast and plants1,2, but their existence in mammals remains controversial3-5. H...

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Main Authors: Luongo, Timothy (Author) , Eller, Jared M. (Author) , Lu, Mu-Jie (Author) , Niere, Marc (Author) , Raith, Fabio (Author) , Perry, Caroline (Author) , Bornstein, Marc R. (Author) , Oliphint, Paul (Author) , Wang, Lin (Author) , McReynolds, Melanie R. (Author) , Migaud, Marie E. (Author) , Rabinowitz, Joshua D. (Author) , Johnson, F. Brad (Author) , Johnsson, Kai (Author) , Ziegler, Mathias (Author) , Cambronne, Xiaolu A. (Author) , Baur, Joseph A. (Author)
Format: Article (Journal)
Language:English
Published: 03 December 2020
In: Nature
Year: 2020, Volume: 588, Pages: 174-179
ISSN:1476-4687
DOI:10.1038/s41586-020-2741-7
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/s41586-020-2741-7
Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/s41586-020-2741-7
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Author Notes:Timothy S. Luongo, Jared M. Eller, Mu-Jie Lu, Marc Niere, Fabio Raith, Caroline Perry, Marc R. Bornstein, Paul Oliphint, Lin Wang, Melanie R. McReynolds, Marie E. Migaud, Joshua D. Rabinowitz, F. Brad Johnson, Kai Johnsson, Mathias Ziegler, Xiaolu A. Cambronne & Joseph A. Baur
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Summary:Mitochondria require nicotinamide adenine dinucleotide (NAD+) to carry out the fundamental processes that fuel respiration and mediate cellular energy transduction. Mitochondrial NAD+ transporters have been identified in yeast and plants1,2, but their existence in mammals remains controversial3-5. Here we demonstrate that mammalian mitochondria can take up intact NAD+, and identify SLC25A51 (also known as MCART1)—an essential6,7 mitochondrial protein of previously unknown function—as a mammalian mitochondrial NAD+ transporter. Loss of SLC25A51 decreases mitochondrial—but not whole-cell—NAD+ content, impairs mitochondrial respiration, and blocks the uptake of NAD+ into isolated mitochondria. Conversely, overexpression of SLC25A51 or SLC25A52 (a nearly identical paralogue of SLC25A51) increases mitochondrial NAD+ levels and restores NAD+ uptake into yeast mitochondria lacking endogenous NAD+ transporters. Together, these findings identify SLC25A51 as a mammalian transporter capable of importing NAD+ into mitochondria.
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Physical Description:Online Resource
ISSN:1476-4687
DOI:10.1038/s41586-020-2741-7

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