NRK1 controls nicotinamide mononucleotide and nicotinamide riboside metabolism in mammalian cells
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Standard
NRK1 controls nicotinamide mononucleotide and nicotinamide riboside metabolism in mammalian cells. / Ratajczak, Joanna; Joffraud, Magali; Trammell, Samuel A.J.; Ras, Rosa; Canela, Nuria; Boutant, Marie; Kulkarni, Sameer S.; Rodrigues, Marcelo; Redpath, Philip; Migaud, Marie E.; Auwerx, Johan; Yanes, Oscar; Brenner, Charles; Cantó, Carles.
I: Nature Communications, Bind 7, 13103, 11.10.2016.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - NRK1 controls nicotinamide mononucleotide and nicotinamide riboside metabolism in mammalian cells
AU - Ratajczak, Joanna
AU - Joffraud, Magali
AU - Trammell, Samuel A.J.
AU - Ras, Rosa
AU - Canela, Nuria
AU - Boutant, Marie
AU - Kulkarni, Sameer S.
AU - Rodrigues, Marcelo
AU - Redpath, Philip
AU - Migaud, Marie E.
AU - Auwerx, Johan
AU - Yanes, Oscar
AU - Brenner, Charles
AU - Cantó, Carles
PY - 2016/10/11
Y1 - 2016/10/11
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84991294515&partnerID=8YFLogxK
U2 - 10.1038/ncomms13103
DO - 10.1038/ncomms13103
M3 - Journal article
C2 - 27725675
AN - SCOPUS:84991294515
VL - 7
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 13103
ER -
ID: 220855065