SLC25A51 is a mammalian mitochondrial NAD+ transporter

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.