NRK1 controls nicotinamide mononucleotide and nicotinamide riboside metabolism in mammalian cells

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 Yanes, Charles Brenner () and Carles Cantó ()
Additional contact information
Joanna Ratajczak: Nestlé Institute of Health Sciences (NIHS)
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
Núria Canela: Group of Research on Omic Methodologies (GROM), 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
Philip Redpath: School of Pharmacy, Queen’s University Belfast
Marie E. Migaud: Carver College of Medicine, University of Iowa
Johan Auwerx: Laboratory of Integrative and Systems Physiology, Ecole Polytechnique Fédérale de Lausanne (EPFL)
Oscar Yanes: Centre for Omic Sciences, Universitat Rovira i Virgili
Charles Brenner: Carver College of Medicine, University of Iowa
Carles Cantó: Nestlé Institute of Health Sciences (NIHS)

Nature Communications, 2016, vol. 7, issue 1, 1-12

Abstract: 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.

Date: 2016
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/ncomms13103 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13103

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms13103

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().