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SLC25A51 is a mammalian mitochondrial NAD(+) transporter

Mitochondria require nicotinamide adenine dinucleotide (NAD(+)) in order to carry out the fundamental processes that fuel respiration and mediate cellular energy transduction. Mitochondrial NAD(+) transporters have been identified in yeast and plants (1,2) but their very existence is controversial i...

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Autores principales: Luongo, Timothy S., Eller, Jared M., Lu, Mu-Jie, Niere, Marc, Raith, Fabio, Perry, Caroline, Bornstein, Marc R., Oliphint, Paul, Wang, Lin, McReynolds, Melanie R., Migaud, Marie E., Rabinowitz, Joshua D., Johnson, F. Brad, Johnsson, Kai, Ziegler, Mathias, Cambronne, Xiaolu A., Baur, Joseph A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7718333/
https://www.ncbi.nlm.nih.gov/pubmed/32906142
http://dx.doi.org/10.1038/s41586-020-2741-7
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author Luongo, Timothy S.
Eller, Jared M.
Lu, Mu-Jie
Niere, Marc
Raith, Fabio
Perry, Caroline
Bornstein, Marc R.
Oliphint, Paul
Wang, Lin
McReynolds, Melanie R.
Migaud, Marie E.
Rabinowitz, Joshua D.
Johnson, F. Brad
Johnsson, Kai
Ziegler, Mathias
Cambronne, Xiaolu A.
Baur, Joseph A.
author_facet Luongo, Timothy S.
Eller, Jared M.
Lu, Mu-Jie
Niere, Marc
Raith, Fabio
Perry, Caroline
Bornstein, Marc R.
Oliphint, Paul
Wang, Lin
McReynolds, Melanie R.
Migaud, Marie E.
Rabinowitz, Joshua D.
Johnson, F. Brad
Johnsson, Kai
Ziegler, Mathias
Cambronne, Xiaolu A.
Baur, Joseph A.
author_sort Luongo, Timothy S.
collection PubMed
description Mitochondria require nicotinamide adenine dinucleotide (NAD(+)) in order to carry out the fundamental processes that fuel respiration and mediate cellular energy transduction. Mitochondrial NAD(+) transporters have been identified in yeast and plants (1,2) but their very existence is controversial in mammals (3–5). Here we demonstrate that mammalian mitochondria are capable of taking up intact NAD(+) and identify SLC25A51 (an essential (6,7) mitochondrial protein of previously unknown function, also known as MCART1) 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 a nearly identical paralog, SLC25A52, increases mitochondrial NAD(+) levels and restores NAD(+) uptake into yeast mitochondria lacking endogenous NAD(+) transporters. Together, these findings identify SLC25A51 as the first transporter capable of importing NAD(+) into mammalian mitochondria.
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spelling pubmed-77183332021-03-09 SLC25A51 is a mammalian mitochondrial NAD(+) transporter Luongo, Timothy S. Eller, Jared M. Lu, Mu-Jie Niere, Marc Raith, Fabio Perry, Caroline Bornstein, Marc R. Oliphint, Paul Wang, Lin McReynolds, Melanie R. Migaud, Marie E. Rabinowitz, Joshua D. Johnson, F. Brad Johnsson, Kai Ziegler, Mathias Cambronne, Xiaolu A. Baur, Joseph A. Nature Article Mitochondria require nicotinamide adenine dinucleotide (NAD(+)) in order to carry out the fundamental processes that fuel respiration and mediate cellular energy transduction. Mitochondrial NAD(+) transporters have been identified in yeast and plants (1,2) but their very existence is controversial in mammals (3–5). Here we demonstrate that mammalian mitochondria are capable of taking up intact NAD(+) and identify SLC25A51 (an essential (6,7) mitochondrial protein of previously unknown function, also known as MCART1) 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 a nearly identical paralog, SLC25A52, increases mitochondrial NAD(+) levels and restores NAD(+) uptake into yeast mitochondria lacking endogenous NAD(+) transporters. Together, these findings identify SLC25A51 as the first transporter capable of importing NAD(+) into mammalian mitochondria. 2020-09-09 2020-12 /pmc/articles/PMC7718333/ /pubmed/32906142 http://dx.doi.org/10.1038/s41586-020-2741-7 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Luongo, Timothy S.
Eller, Jared M.
Lu, Mu-Jie
Niere, Marc
Raith, Fabio
Perry, Caroline
Bornstein, Marc R.
Oliphint, Paul
Wang, Lin
McReynolds, Melanie R.
Migaud, Marie E.
Rabinowitz, Joshua D.
Johnson, F. Brad
Johnsson, Kai
Ziegler, Mathias
Cambronne, Xiaolu A.
Baur, Joseph A.
SLC25A51 is a mammalian mitochondrial NAD(+) transporter
title SLC25A51 is a mammalian mitochondrial NAD(+) transporter
title_full SLC25A51 is a mammalian mitochondrial NAD(+) transporter
title_fullStr SLC25A51 is a mammalian mitochondrial NAD(+) transporter
title_full_unstemmed SLC25A51 is a mammalian mitochondrial NAD(+) transporter
title_short SLC25A51 is a mammalian mitochondrial NAD(+) transporter
title_sort slc25a51 is a mammalian mitochondrial nad(+) transporter
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7718333/
https://www.ncbi.nlm.nih.gov/pubmed/32906142
http://dx.doi.org/10.1038/s41586-020-2741-7
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