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Slc12a8 is a nicotinamide mononucleotide transporter.
Alessia Grozio1, Kathryn F Mills1, Jun Yoshino2
1Department of Developmental Biology, Washington University School of Medicine,, St. Louis, MO 63110, USA.
Nature Metabolism
|May 28, 2019
Summary
Scientists discovered Slc12a8 as the first specific transporter for nicotinamide mononucleotide (NMN). This transporter is crucial for NMN uptake and maintaining NAD+ levels in the intestine, especially during aging.
Area of Science:
- Biochemistry
- Cell Biology
- Molecular Biology
Background:
- Nicotinamide mononucleotide (NMN) is a key precursor for NAD+ synthesis.
- NAD+ levels decline with age, contributing to age-related diseases.
- The cellular uptake mechanism for NMN remained largely unknown.
Purpose of the Study:
- To identify the specific transporter responsible for cellular uptake of NMN.
- To investigate the role of this transporter in intestinal NAD+ metabolism and aging.
Main Methods:
- Gene expression analysis of Slc12a8 in murine small intestine.
- In vitro and in vivo knockdown experiments to assess NMN uptake.
- Isotopic tracing of NMN uptake in Slc12a8 deficient mice.
- Analysis of NAD+ levels in jejunum and ileum.
Main Results:
- The Slc12a8 gene encodes a specific transporter for NMN.
- Slc12a8 is highly expressed in the murine small intestine and regulated by NAD+.
- Slc12a8 knockdown significantly reduces NMN uptake in vitro and in vivo.
- Slc12a8 deficiency leads to decreased NAD+ levels in the jejunum and ileum.
- Slc12a8 expression is upregulated in aged murine ileum, aiding NAD+ maintenance.
Conclusions:
- Slc12a8 is identified as the first specific NMN transporter.
- Slc12a8 plays a critical role in intestinal NAD+ metabolism.
- Slc12a8 contributes to maintaining NAD+ levels in the aging intestine.
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