Saccharomyces cerevisiae YOR071C encodes the high affinity nicotinamide riboside transporter Nrt1.
NAD(+) is an essential coenzyme for hydride transfer enzymes and a substrate of sirtuins and other NAD(+)-consuming enzymes. Nicotinamide riboside is a recently discovered eukaryotic NAD(+) precursor converted to NAD(+) via the nicotinamide riboside kinase pathway and by nucleosidase activity and nicotinamide salvage. Nicotinamide riboside supplementation of yeast extends replicative life span on high glucose medium. The molecular basis for nicotinamide riboside uptake was unknown in any eukaryote. Here, we show that deletion of a single gene, YOR071C, abrogates nicotinamide riboside uptake without altering nicotinic acid or nicotinamide import. The gene, which is negatively regulated by Sum1, Hst1, and Rfm1, fully restores nicotinamide riboside import and utilization when resupplied to mutant yeast cells. The encoded polypeptide, Nrt1, is a predicted deca-spanning membrane protein related to the thiamine transporter, which functions as a pH-dependent facilitator with a K(m) for nicotinamide riboside of 22 microm. Nrt1-related molecules are conserved in particular fungi, suggesting a similar basis for nicotinamide riboside uptake.
Belenky
Peter A
PA
Department of Genetics and the Norris Cotton Cancer Center, Dartmouth Medical School, Lebanon, NH 03756, USA.
Moga
Tiberiu G
TG
Brenner
Charles
C
D001692:Biological Transport; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D009243:NAD / Q000378:metabolism; D009536:Niacinamide / Q000031:analogs & derivatives / Q000378:metabolism; D033703:Nucleoside Transport Proteins; D011485:Protein Binding; D011726:Pyridinium Compounds; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
D026901:Membrane Transport Proteins; C528866:Nrt1 protein, S cerevisiae; D033703:Nucleoside Transport Proteins; D011726:Pyridinium Compounds; D029701:Saccharomyces cerevisiae Proteins; C018613:nicotinamide-beta-riboside; D009243:NAD; D009536:Niacinamide