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. SLC25A51 is identified as a transporter of intact NAD + into mammalian mitochondria and is required to maintain the mitochondrial NAD + pool and respiratory function.