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Saccharomyces cerevisiae YOR071C encodes the high affinity nicotinamide riboside transporter Nrt1
Journal article   Open access   Peer reviewed

Saccharomyces cerevisiae YOR071C encodes the high affinity nicotinamide riboside transporter Nrt1

Peter A Belenky, Tiberiu G Moga and Charles Brenner
The Journal of biological chemistry, Vol.283(13), pp.8075-8079
03/28/2008
DOI: 10.1074/jbc.C800021200
PMID: 18258590
url
https://doi.org/10.1074/jbc.C800021200View
Published (Version of record) Open Access

Abstract

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.
 Niacinamide - analogs & derivatives Niacinamide - metabolism Saccharomyces cerevisiae - genetics Saccharomyces cerevisiae Proteins - genetics Mutation - genetics Saccharomyces cerevisiae - metabolism Biological Transport Membrane Transport Proteins - genetics Nucleoside Transport Proteins Saccharomyces cerevisiae Proteins - metabolism Protein Binding Membrane Transport Proteins - metabolism Kinetics NAD - metabolism Hydrogen-Ion Concentration

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