Journal article
NRK1 controls nicotinamide mononucleotide and nicotinamide riboside metabolism in mammalian cells
Nature communications, Vol.7(1), 13103
10/11/2016
DOI: 10.1038/ncomms13103
PMCID: PMC5476803
PMID: 27725675
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.
Details
- Title: Subtitle
- NRK1 controls nicotinamide mononucleotide and nicotinamide riboside metabolism in mammalian cells
- Creators
- Joanna Ratajczak - School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne CH-1015, SwitzerlandMagali Joffraud - Nestlé Institute of Health Sciences (NIHS), Lausanne CH-1015, SwitzerlandSamuel A J Trammell - Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USARosa Ras - Centre for Omic Sciences, Universitat Rovira i Virgili, Reus 43204, SpainNúria Canela - Centre for Omic Sciences, Universitat Rovira i Virgili, Reus 43204, SpainMarie Boutant - Nestlé Institute of Health Sciences (NIHS), Lausanne CH-1015, SwitzerlandSameer S Kulkarni - Nestlé Institute of Health Sciences (NIHS), Lausanne CH-1015, SwitzerlandMarcelo Rodrigues - School of Pharmacy, Queen's University Belfast, Belfast BT7 1NN, UKPhilip Redpath - School of Pharmacy, Queen's University Belfast, Belfast BT7 1NN, UKMarie E Migaud - School of Pharmacy, Queen's University Belfast, Belfast BT7 1NN, UKJohan Auwerx - Laboratory of Integrative and Systems Physiology, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne CH-1015, SwitzerlandOscar Yanes - Department of Electronic Engineering, Universitat Rovira i Virgili, Tarragona 43007, SpainCharles Brenner - Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USACarles Cantó - School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne CH-1015, Switzerland
- Resource Type
- Journal article
- Publication Details
- Nature communications, Vol.7(1), 13103
- DOI
- 10.1038/ncomms13103
- PMID
- 27725675
- PMCID
- PMC5476803
- NLM abbreviation
- Nat Commun
- ISSN
- 2041-1723
- eISSN
- 2041-1723
- Publisher
- England
- Grant note
- R21 AA022371 / NIAAA NIH HHS R01 HL108379 / NHLBI NIH HHS
- Language
- English
- Date published
- 10/11/2016
- Academic Unit
- Biochemistry and Molecular Biology; Internal Medicine
- Record Identifier
- 9983788429802771
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