Ratajczak J Joffraud M Trammell SA Ras R Canela N Boutant M Kulkarni SS Rodrigues M Redpath P Migaud ME Auwerx J Yanes O Brenner C Cantó C 2016 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. application/pdf https://sonar.ch/global/documents/163025 eng info:eu-repo/semantics/altIdentifier/doi/10.1038/ncomms13103 info:eu-repo/semantics/altIdentifier/pmid/27725675 info:eu-repo/semantics/openAccess Nature communications. - 2016 Animals Hep G2 Cells Hepatocytes Humans Injections, Intraperitoneal Mammals Mice, Knockout NAD Niacinamide Nicotinamide Mononucleotide Phosphotransferases (Alcohol Group Acceptor) NRK1 controls nicotinamide mononucleotide and nicotinamide riboside metabolism in mammalian cells. http://purl.org/coar/resource_type/c_6501