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 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.