SLC25A51 is a mammalian mitochondrial NAD+ transporter

Nature. 2020 Dec;588(7836):174-179. doi: 10.1038/s41586-020-2741-7. Epub 2020 Sep 9.

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 plants1,2, but their existence in mammals remains controversial3-5. Here we demonstrate that mammalian mitochondria can take up intact NAD+, and identify SLC25A51 (also known as MCART1)-an essential6,7 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Transport
  • Cell Line
  • Cell Respiration / genetics
  • Genetic Complementation Test
  • Humans
  • Mice
  • Mitochondria / genetics
  • Mitochondria / metabolism*
  • Mitochondria / pathology
  • Mitochondrial Proteins / deficiency
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism*
  • NAD / metabolism*
  • Nucleotide Transport Proteins / genetics
  • Organic Cation Transport Proteins / deficiency
  • Organic Cation Transport Proteins / genetics
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics

Substances

  • Mitochondrial Proteins
  • Ndt1 protein, S cerevisiae
  • Nucleotide Transport Proteins
  • Organic Cation Transport Proteins
  • Saccharomyces cerevisiae Proteins
  • NAD