Assimilation of Endogenous Nicotinamide Riboside Is Essential for Calorie Restriction-mediated Life Span Extension in Saccharomyces cerevisiae
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NAD(+) (nicotinamide adenine dinucleotide) is an essential cofactor involved in various biological processes including calorie restriction-mediated life span extension. Administration of nicotinamide riboside (NmR) has been shown to ameliorate deficiencies related to aberrant NAD(+) metabolism in both yeast and mammalian cells. However, the biological role of endogenous NmR remains unclear. Here we demonstrate that salvaging endogenous NmR is an integral part of NAD(+) metabolism. A balanced NmR salvage cycle is essential for calorie restriction-induced life span extension and stress resistance in yeast. Our results also suggest that partitioning of the pyridine nucleotide flux between the classical salvage cycle and the NmR salvage branch might be modulated by the NAD(+)-dependent Sir2 deacetylase. Furthermore, two novel deamidation steps leading to nicotinic acid mononucleotide and nicotinic acid riboside production are also uncovered that further underscore the complexity and flexibility of NAD(+) metabolism. In addition, utilization of extracellular nicotinamide mononucleotide requires prior conversion to NmR mediated by a periplasmic phosphatase Pho5. Conversion to NmR may thus represent a strategy for the transport and assimilation of large nonpermeable NAD(+) precursors. Together, our studies provide a molecular basis for how NAD(+) homeostasis factors confer metabolic flexibility.
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Extracellular dephosphorylation of NMN into NR is necessary for its utilization in yeast.
“While extracellular dephosphorylation of NMN into NR is necessary for its utilization in yeast34”
From NRK1 controls nicotinamide mononucleotide and nicotinamide riboside metabolism in mammalian cells (2016) · cites this paper as [34]
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- Authors
- Lu, S.-P., Kato, M., & Lin, S.-J.
- Affiliations
- University of California, Davis (US)
- Corresponding author
- Lin, Su-Ju
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2009-06
- Volume
- 284
- Issue
- 25
- Pages
- 17110-17119
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC2719349
- OpenAlex
- W2030392188
- Cited by
- 75
- References
- 49
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 3 · 2023: 2 · 2022: 5 · 2021: 4 · 2020: 3 · 2019: 3 · 2018: 4 · 2017: 7 · 2016: 3 · 2015: 7 · 2014: 4 · 2013: 6 · 2012: 6
- FWCI
- 4.50
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (R01AG024351)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- nicotinamide riboside, NAD+ metabolism, caloric restriction, lifespan extension, Saccharomyces cerevisiae, nicotinic acid mononucleotide, nicotinamide mononucleotide, stress tolerance, NAD+ homeostasis
- MeSH terms
- Animals, Genes, Fungal, Hot Temperature, Histone Deacetylases, Longevity, Mammals, Models, Biological, Mutation, NAD, Niacinamide, N-Glycosyl Hydrolases, Pentosyltransferases, Pyridinium Compounds, Saccharomyces cerevisiae, Stress, Physiological, Time Factors, Saccharomyces cerevisiae Proteins, Caloric Restriction, Sirtuins, Silent Information Regulator Proteins, Saccharomyces cerevisiae, Sirtuin 2
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