TY - JOUR
T1 - SLC25A51 is a mammalian mitochondrial NAD+ transporter
AU - Luongo, Timothy S.
AU - Eller, Jared M.
AU - Lu, Mu Jie
AU - Niere, Marc
AU - Raith, Fabio
AU - Perry, Caroline
AU - Bornstein, Marc R.
AU - Oliphint, Paul
AU - Wang, Lin
AU - McReynolds, Melanie R.
AU - Migaud, Marie E.
AU - Rabinowitz, Joshua D.
AU - Johnson, F. Brad
AU - Johnsson, Kai
AU - Ziegler, Mathias
AU - Cambronne, Xiaolu A.
AU - Baur, Joseph A.
N1 - Funding Information:
Acknowledgements We thank all members of the Baur and Cambronne laboratories, V. Moiseenkova-Bell, A. Ellington, E. Marcotte, R. Goodman, I. Heiland, M. Whorton, E. Gouaux and J. Dixon for constructive discussions and suggestions; and M. Blair, Q. Chen, V. Annamalai, X. Yu, A. Slepian and CBRS UT Austin Proteomics Facility for technical support. This work was supported by grants from the National Institutes of Health (R01DK098656 to J.A.B., DP2GM126897 to X.A.C., TL1TR001880, T32AR53461 and F32HL145923 to T.S.L.) and the Norwegian Research Council (250395/F20 to M.Z.).
Publisher Copyright:
© 2020, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2020/12/3
Y1 - 2020/12/3
N2 - 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.
AB - 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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U2 - 10.1038/s41586-020-2741-7
DO - 10.1038/s41586-020-2741-7
M3 - Article
C2 - 32906142
AN - SCOPUS:85090431624
SN - 0028-0836
VL - 588
SP - 174
EP - 179
JO - Nature
JF - Nature
IS - 7836
ER -