Back
Full-text
Journal article

NRK1 controls nicotinamide mononucleotide and nicotinamide riboside metabolism in mammalian cells.

  • Ratajczak J Nestlé Institute of Health Sciences (NIHS), Lausanne CH-1015, Switzerland.
  • Joffraud M Nestlé Institute of Health Sciences (NIHS), Lausanne CH-1015, Switzerland.
  • Trammell SA Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA.
  • Ras R Group of Research on Omic Methodologies (GROM), Universitat Rovira i Virgili, Reus 43204, Spain.
  • Canela N Group of Research on Omic Methodologies (GROM), Universitat Rovira i Virgili, Reus 43204, Spain.
  • Boutant M Nestlé Institute of Health Sciences (NIHS), Lausanne CH-1015, Switzerland.
  • Kulkarni SS Nestlé Institute of Health Sciences (NIHS), Lausanne CH-1015, Switzerland.
  • Rodrigues M Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA.
  • Redpath P School of Pharmacy, Queen's University Belfast, Belfast BT7 1NN, UK.
  • Migaud ME Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA.
  • Auwerx J Laboratory of Integrative and Systems Physiology, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne CH-1015, Switzerland.
  • Yanes O Centre for Omic Sciences, Universitat Rovira i Virgili, Reus 43204, Spain.
  • Brenner C Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA.
  • Cantó C Nestlé Institute of Health Sciences (NIHS), Lausanne CH-1015, Switzerland.
Show more…
  • 2016-10-12
Published in:
  • Nature communications. - 2016
Animals
Hep G2 Cells
Hepatocytes
Humans
Injections, Intraperitoneal
Mammals
Mice, Knockout
NAD
Niacinamide
Nicotinamide Mononucleotide
Phosphotransferases (Alcohol Group Acceptor)
English NAD+ is a vital redox cofactor and a substrate required for activity of various enzyme families, including sirtuins and poly(ADP-ribose) polymerases. Supplementation with NAD+ precursors, such as nicotinamide mononucleotide (NMN) or nicotinamide riboside (NR), protects against metabolic disease, neurodegenerative disorders and age-related physiological decline in mammals. Here we show that nicotinamide riboside kinase 1 (NRK1) is necessary and rate-limiting for the use of exogenous NR and NMN for NAD+ synthesis. Using genetic gain- and loss-of-function models, we further demonstrate that the role of NRK1 in driving NAD+ synthesis from other NAD+ precursors, such as nicotinamide or nicotinic acid, is dispensable. Using stable isotope-labelled compounds, we confirm NMN is metabolized extracellularly to NR that is then taken up by the cell and converted into NAD+. Our results indicate that mammalian cells require conversion of extracellular NMN to NR for cellular uptake and NAD+ synthesis, explaining the overlapping metabolic effects observed with the two compounds.
Language
  • English
Open access status
gold
Identifiers
Persistent URL
https://sonar.ch/global/documents/163025
Statistics
Document views: 29 File downloads:
  • Full-text: 0