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Nat Metab. 2019 Jan;1(1):47-57. doi: 10.1038/s42255-018-0009-4. Epub 2019 Jan 7.

Slc12a8 is a nicotinamide mononucleotide transporter.

Author information

1
Department of Developmental Biology, Washington University School of Medicine,, St. Louis, MO 63110, USA.
2
Center for Human Nutrition, Division of Geriatrics and Nutritional Science, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
3
Department of Experimental Medicine, Section of Biochemistry, and Center of Excellence for Biomedical Research, University of Genova, 1 16132 Genova, Italy.
4
Mitchell Cancer Institute, University of South Alabama, Mobile, AL 36606, USA.
5
Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110, USA.

Abstract

Nicotinamide mononucleotide (NMN) is a biosynthetic precursor of NAD+ known to promote cellular NAD+ production and counteract age-associated pathologies associated with a decline in tissue NAD+ levels. How NMN is taken up into cells has not been entirely clear. Here we show that the Slc12a8 gene encodes a specific NMN transporter. We find that Slc12a8 is highly expressed and regulated by NAD+ in the murine small intestine. Slc12a8 knockdown abrogates the uptake of NMN in vitro and in vivo. We further show that Slc12a8 specifically transports NMN, but not nicotinamide riboside, and that NMN transport depends on the presence of sodium ion. Slc12a8 deficiency significantly decreases NAD+ levels in the jejunum and ileum, which is associated with reduced NMN uptake as traced by doubly labeled isotopic NMN. Finally, we observe that Slc12a8 expression is upregulated in the aged murine ileum, which contributes to the maintenance of ileal NAD+ levels. Our work identifies the first NMN transporter and demonstrates that Slc12a8 has a critical role in regulating intestinal NAD+ metabolism.

PMID:
31131364
PMCID:
PMC6530925
[Available on 2019-07-07]
DOI:
10.1038/s42255-018-0009-4

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