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J. Biol. Chem., Vol. 283, Issue 13, 8075-8079, March 28, 2008

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Saccharomyces cerevisiae YOR071C Encodes the High Affinity Nicotinamide Riboside Transporter Nrt1^*

From the Departments of Genetics and Biochemistry and the Norris Cotton Cancer Center, Dartmouth Medical School, Lebanon, New Hampshire 03756

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 µM. Nrt1-related molecules are conserved in particular fungi, suggesting a similar basis for nicotinamide riboside uptake.

Received for publication, January 28, 2008 , and in revised form, February 5, 2008.

^* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains a supplemental table.

This paper is dedicated to the memory of Professor Arthur Kornberg, pioneer in NAD⁺ metabolism.

¹ Supported by a John H. Copenhaver, Jr., and William H. Thomas, M.D., 1952 Fellowship from the Dartmouth Graduate Office.

² Supported by a presidential fellowship from Dartmouth College.

³ To whom correspondence should be addressed. E-mail: charles.brenner{at}dartmouth.edu.

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