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NRK1 controls nicotinamide mononucleotide and nicotinamide riboside metabolism in mammalian cells

Author

Listed:
  • Joanna Ratajczak

    (Nestlé Institute of Health Sciences (NIHS)
    School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL))

  • Magali Joffraud

    (Nestlé Institute of Health Sciences (NIHS))

  • Samuel A. J. Trammell

    (Carver College of Medicine, University of Iowa)

  • Rosa Ras

    (Group of Research on Omic Methodologies (GROM), Universitat Rovira i Virgili
    Centre for Omic Sciences, Universitat Rovira i Virgili)

  • Núria Canela

    (Group of Research on Omic Methodologies (GROM), Universitat Rovira i Virgili
    Centre for Omic Sciences, Universitat Rovira i Virgili)

  • Marie Boutant

    (Nestlé Institute of Health Sciences (NIHS))

  • Sameer S. Kulkarni

    (Nestlé Institute of Health Sciences (NIHS))

  • Marcelo Rodrigues

    (Carver College of Medicine, University of Iowa
    School of Pharmacy, Queen’s University Belfast)

  • Philip Redpath

    (School of Pharmacy, Queen’s University Belfast)

  • Marie E. Migaud

    (Carver College of Medicine, University of Iowa
    School of Pharmacy, Queen’s University Belfast)

  • Johan Auwerx

    (Laboratory of Integrative and Systems Physiology, Ecole Polytechnique Fédérale de Lausanne (EPFL))

  • Oscar Yanes

    (Centre for Omic Sciences, Universitat Rovira i Virgili
    Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM)
    Universitat Rovira i Virgili)

  • Charles Brenner

    (Carver College of Medicine, University of Iowa)

  • Carles Cantó

    (Nestlé Institute of Health Sciences (NIHS)
    School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL))

Abstract

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.

Suggested Citation

  • Joanna Ratajczak & Magali Joffraud & Samuel A. J. Trammell & Rosa Ras & Núria Canela & Marie Boutant & Sameer S. Kulkarni & Marcelo Rodrigues & Philip Redpath & Marie E. Migaud & Johan Auwerx & Oscar , 2016. "NRK1 controls nicotinamide mononucleotide and nicotinamide riboside metabolism in mammalian cells," Nature Communications, Nature, vol. 7(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13103
    DOI: 10.1038/ncomms13103
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    Cited by:

    1. Miyuki Nomura & Mai Ohuchi & Yoshimi Sakamoto & Kei Kudo & Keisuke Yaku & Tomoyoshi Soga & Yuki Sugiura & Mami Morita & Kayoko Hayashi & Shuko Miyahara & Taku Sato & Yoji Yamashita & Shigemi Ito & Nao, 2023. "Niacin restriction with NAMPT-inhibition is synthetic lethal to neuroendocrine carcinoma," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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