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Slc12a8 is a nicotinamide mononucleotide transporter

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 g...

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Autores principales: Grozio, Alessia, Mills, Kathryn F., Yoshino, Jun, Bruzzone, Santina, Sociali, Giovanna, Tokizane, Kyohei, Lei, Hanyue Cecilia, Cunningham, Richard, Sasaki, Yo, Migaud, Marie E., Imai, Shin-ichiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6530925/
https://www.ncbi.nlm.nih.gov/pubmed/31131364
http://dx.doi.org/10.1038/s42255-018-0009-4
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author Grozio, Alessia
Mills, Kathryn F.
Yoshino, Jun
Bruzzone, Santina
Sociali, Giovanna
Tokizane, Kyohei
Lei, Hanyue Cecilia
Cunningham, Richard
Sasaki, Yo
Migaud, Marie E.
Imai, Shin-ichiro
author_facet Grozio, Alessia
Mills, Kathryn F.
Yoshino, Jun
Bruzzone, Santina
Sociali, Giovanna
Tokizane, Kyohei
Lei, Hanyue Cecilia
Cunningham, Richard
Sasaki, Yo
Migaud, Marie E.
Imai, Shin-ichiro
author_sort Grozio, Alessia
collection PubMed
description 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.
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spelling pubmed-65309252019-07-07 Slc12a8 is a nicotinamide mononucleotide transporter Grozio, Alessia Mills, Kathryn F. Yoshino, Jun Bruzzone, Santina Sociali, Giovanna Tokizane, Kyohei Lei, Hanyue Cecilia Cunningham, Richard Sasaki, Yo Migaud, Marie E. Imai, Shin-ichiro Nat Metab Article 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. 2019-01-07 2019-01 /pmc/articles/PMC6530925/ /pubmed/31131364 http://dx.doi.org/10.1038/s42255-018-0009-4 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Grozio, Alessia
Mills, Kathryn F.
Yoshino, Jun
Bruzzone, Santina
Sociali, Giovanna
Tokizane, Kyohei
Lei, Hanyue Cecilia
Cunningham, Richard
Sasaki, Yo
Migaud, Marie E.
Imai, Shin-ichiro
Slc12a8 is a nicotinamide mononucleotide transporter
title Slc12a8 is a nicotinamide mononucleotide transporter
title_full Slc12a8 is a nicotinamide mononucleotide transporter
title_fullStr Slc12a8 is a nicotinamide mononucleotide transporter
title_full_unstemmed Slc12a8 is a nicotinamide mononucleotide transporter
title_short Slc12a8 is a nicotinamide mononucleotide transporter
title_sort slc12a8 is a nicotinamide mononucleotide transporter
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6530925/
https://www.ncbi.nlm.nih.gov/pubmed/31131364
http://dx.doi.org/10.1038/s42255-018-0009-4
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