SLC25A51 is a mammalian mitochondrial NAD transporter.

TitleSLC25A51 is a mammalian mitochondrial NAD transporter.
Publication TypeJournal Article
Year of Publication2020
AuthorsLuongo, TS, Eller, JM, Lu, M-J, Niere, M, Raith, F, Perry, C, Bornstein, MR, Oliphint, P, Wang, L, McReynolds, MR, Migaud, ME, Rabinowitz, JD, F Johnson, B, Johnsson, K, Ziegler, M, Cambronne, XA, Baur, JA
JournalNature
Volume588
Issue7836
Pagination174-179
Date Published2020 12
ISSN1476-4687
KeywordsAnimals, Biological Transport, Cell Line, Cell Respiration, Genetic Complementation Test, Humans, Mice, Mitochondria, Mitochondrial Proteins, NAD, Nucleotide Transport Proteins, Organic Cation Transport Proteins, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins
Abstract

<p>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 plants, but their existence in mammals remains controversial. Here we demonstrate that mammalian mitochondria can take up intact NAD, and identify SLC25A51 (also known as MCART1)-an essential 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.</p>

DOI10.1038/s41586-020-2741-7
Alternate JournalNature
PubMed ID32906142
PubMed Central IDPMC7718333
Grant ListR01 DK098656 / DK / NIDDK NIH HHS / United States
F32 HL145923 / HL / NHLBI NIH HHS / United States
DP2 GM126897 / GM / NIGMS NIH HHS / United States
T32 AR053461 / AR / NIAMS NIH HHS / United States
TL1 TR001880 / TR / NCATS NIH HHS / United States
P30 DK019525 / DK / NIDDK NIH HHS / United States