Luongo 2020 Nature

Luongo TS, Eller JM, Lu MJ, Niere M, Raith F, Perry C, Bornstein MR, Oliphint P, Wang L, McReynolds MR, Migaud ME, Rabinowitz JD, Johnson FB, Johnsson K, Ziegler M, Cambronne XA, Baur JA (2020) SLC25A51 is a mammalian mitochondrial NAD+ transporter. https://doi.org/10.1038/s41586-020-2741-7

» Nature 588:174-79. PMID: 32906142 Open Access

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 (2020) Nature

Abstract: 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^1,2, but their existence in mammals remains controversial^3-5. Here we demonstrate that mammalian mitochondria can take up intact NAD⁺, and identify SLC25A51 (also known as MCART1)-an essential^6,7 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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2023-10