| Literature DB >> 32906142 |
Timothy S Luongo1, Jared M Eller2, Mu-Jie Lu2, Marc Niere3, Fabio Raith4,5, Caroline Perry1, Marc R Bornstein1, Paul Oliphint2, Lin Wang6, Melanie R McReynolds6, Marie E Migaud7, Joshua D Rabinowitz6, F Brad Johnson8, Kai Johnsson4,9, Mathias Ziegler3, Xiaolu A Cambronne10, Joseph A Baur11.
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 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.Entities:
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Year: 2020 PMID: 32906142 PMCID: PMC7718333 DOI: 10.1038/s41586-020-2741-7
Source DB: PubMed Journal: Nature ISSN: 0028-0836 Impact factor: 49.962