SLC25A51 is a mammalian mitochondrial NAD+ transporter

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

Research output: Contribution to journalArticle

Abstract

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 plants1,2 but their very existence is controversial in mammals3–5. Here we demonstrate that mammalian mitochondria are capable of taking up intact NAD+ and identify SLC25A51 (an essential6,7 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.

Original languageEnglish (US)
JournalNature
DOIs
StateAccepted/In press - 2020

All Science Journal Classification (ASJC) codes

  • General

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    Luongo, T. S., Eller, J. M., Lu, M. J., Niere, M., Raith, F., Perry, C., Bornstein, M. R., Oliphint, P., Wang, L., McReynolds, M. R., Migaud, M. E., Rabinowitz, J. D., Johnson, F. B., Johnsson, K., Ziegler, M., Cambronne, X. A., & Baur, J. A. (Accepted/In press). SLC25A51 is a mammalian mitochondrial NAD+ transporter. Nature. https://doi.org/10.1038/s41586-020-2741-7