Mitochondrial nicotinamide adenine dinucleotide transporter SLC25A51
mitochondrion
SLC25A51 is a mammalian mitochondrial NAD<sup>+</sup> transporter.
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> mitochondrial protein of previously unknown function-as a mammalian mitochondrial NAD<sup>+</sup> transporter. Loss of SLC25A51 decreases mitochondrial-but not whole-cell-NAD<sup>+</sup> content, impairs mitochondrial respiration, and blocks the uptake of NAD<sup>+</sup> into isolated mitochondria. Conversely, overexpression of SLC25A51 or SLC25A52 (a nearly identical paralogue of SLC25A51) increases mitochondrial NAD<sup>+</sup> levels and restores NAD<sup>+</sup> uptake into yeast mitochondria lacking endogenous NAD<sup>+</sup> transporters. Together, these findings identify SLC25A51 as a mammalian transporter capable of importing NAD<sup>+</sup> into mitochondria.