Open AccessSLC25A51 is a mammalian mitochondrial NAD+ transporter
Author(s) -
Timothy S. Luongo,
Jared Eller,
Mu Jie Lu,
Marc Niere,
Fabio Raith,
Caroline Perry,
Marc R. Bornstein,
Paul A. Oliphint,
Lin Wang,
Melanie R. McReynolds,
Marie E. Migaud,
Joshua D. Rabinowitz,
F. Brad Johnson,
Kai Johnsson,
Mathias Ziegler,
Xiaolu A. Cambronne,
Joseph A. Baur
Publication year - 2020
Publication title -
nature
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 15.993
H-Index - 1226
eISSN - 1476-4687
pISSN - 0028-0836
DOI - 10.1038/s41586-020-2741-7
Subject(s) - nad+ kinase , mitochondrion , biochemistry , nicotinamide adenine dinucleotide , biology , glycerol 3 phosphate dehydrogenase , transporter , mitochondrial carrier , respiratory chain , microbiology and biotechnology , chemistry , enzyme , gene , bacterial outer membrane , escherichia coli
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.