2. Academic Validation
  3. SLC25A51 is a mammalian mitochondrial NAD+ transporter

SLC25A51 is a mammalian mitochondrial NAD+ transporter

  • Nature. 2020 Dec;588(7836):174-179. doi: 10.1038/s41586-020-2741-7.
Timothy S Luongo 1,  Jared M Eller 2,  Mu-Jie Lu 2,  Marc Niere 3,  Fabio Raith 4 5,  Caroline Perry 1,  Marc R Bornstein 1,  Paul Oliphint 2,  Lin Wang 6,  Melanie R McReynolds 6,  Marie E Migaud 7,  Joshua D Rabinowitz 6,  F Brad Johnson 8,  Kai Johnsson 4 9,  Mathias Ziegler 3,  Xiaolu A Cambronne 10,  Joseph A Baur 11
Affiliations

Affiliations

  • 1 Department of Physiology and Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • 2 Department of Molecular Biosciences, University of Texas at Austin, Austin, TX, USA.
  • 3 Department of Biomedicine, University of Bergen, Bergen, Norway.
  • 4 Department of Chemical Biology, Max Planck Institute for Medical Research, Heidelberg, Germany.
  • 5 Faculty of Chemistry and Earth Sciences, University of Heidelberg, Heidelberg, Germany.
  • 6 Lewis-Sigler Institute for Integrative Genomics, Department of Chemistry, Princeton University, Princeton, NJ, USA.
  • 7 Mitchell Cancer Institute, University of South Alabama, Mobile, AL, USA.
  • 8 Department of Pathology and Laboratory Medicine, Perlman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • 9 Institute of Chemical Sciences and Engineering, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
  • 10 Department of Molecular Biosciences, University of Texas at Austin, Austin, TX, USA. lulu@austin.utexas.edu.
  • 11 Department of Physiology and Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. baur@pennmedicine.upenn.edu.
PMID: 32906142 DOI: 10.1038/s41586-020-2741-7
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.

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