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SLC25A51 is a mammalian mitochondrial NAD+ transporter.


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.

SUBMITTER: Luongo TS 

PROVIDER: S-EPMC7718333 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Mitochondria require nicotinamide adenine dinucleotide (NAD<sup>+</sup>) to carry out the fundamental processes that fuel respiration and mediate cellular energy transduction. Mitochondrial NAD<sup>+</sup> transporters have been identified in yeast and plants<sup>1,2</sup>, but their existence in mammals remains controversial<sup>3-5</sup>. Here we demonstrate that mammalian mitochondria can take up intact NAD<sup>+</sup>, and identify SLC25A51 (also known as MCART1)-an essential<sup>6,7</sup> m  ...[more]

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