ArticleThe Journal of biological chemistry2012
Isonicotinamide enhances Sir2 protein-mediated silencing and longevity in yeast by raising intracellular NAD+ concentration.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 30 citations in OpenAlex.
- Review
- ERC accumulation depletes Sir2 from rDNA and induces cellular senescence by rDNA destabilization.Nucleic acids research · 2025Article
- NADCells · 2025Review
- Exploring the anti-aging potential of natural products and plant extracts in budding yeastF1000Research · 2023Review
- The role of NAD and NAD precursors on longevity and lifespan modulation in the budding yeast, Saccharomyces cerevisiae.Biogerontology · 2022Review
- Deletion of the GAPDH gene contributes to genome stability in Saccharomyces cerevisiae.Scientific reports · 2020Article
- Investigation of the potential regulator proteins associated with the expression of major surface protein and dentilisin inJournal of oral microbiology · 2020Article
- Nicotinamide, Nicotinamide Riboside and Nicotinic Acid-Emerging Roles in Replicative and Chronological Aging in Yeast.Biomolecules · 2020Review
- Role of Nicotinamide Adenine Dinucleotide and Related Precursors as Therapeutic Targets for Age-Related Degenerative Diseases: Rationale, Biochemistry, Pharmacokinetics, and Outcomes.Antioxidants & redox signaling · 2019Review
- Metabonomics onEmerging microbes & infections · 2019Article
- Differences in Sirtuin Regulation in Response to Calorie Restriction in Cryptococcus neoformans.Journal of fungi (Basel, Switzerland) · 2018Article
- Altered Expression of Mitochondrial NADFrontiers in genetics · 2018Article
- Modulation of Replicative Lifespan inFrontiers in microbiology · 2017Article
- The Epigenetic Pathways to Ribosomal DNA Silencing.Microbiology and molecular biology reviews : MMBR · 2016Review
- Intracellular nicotinamide adenine dinucleotide promotes TNF-induced necroptosis in a sirtuin-dependent manner.Cell death and differentiation · 2016Article
- Biotin starvation causes mitochondrial protein hyperacetylation and partial rescue by the SIRT3-like deacetylase Hst4p.Nature communications · 2015Article
- A budding yeast's perspective on aging: the shape I'm in.Experimental biology and medicine (Maywood, N.J.) · 2015Review
- Article
- The β-1,3-glucanosyltransferase Gas1 regulates Sir2-mediated rDNA stability in Saccharomyces cerevisiae.Nucleic acids research · 2014Article
- Yeast sirtuins and the regulation of aging.FEMS yeast research · 2014Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Sirtuins are an evolutionarily conserved family of NAD(+)-dependent protein deacetylases that function in the regulation of gene transcription, cellular metabolism, and aging. Their activity requires the maintenance of an adequate intracellular NAD(+) concentration through the combined action of NAD(+) biosynthesis and salvage pathways. Nicotinamide (NAM) is a key NAD(+) precursor that is also a byproduct and feedback inhibitor of the deacetylation reaction. In Saccharomyces cerevisiae, the nicotinamidase Pnc1 converts NAM to nicotinic acid (NA), which is then used as a substrate by the NAD(+) salvage pathway enzyme NA phosphoribosyltransferase (Npt1). Isonicotinamide (INAM) is an isostere of NAM that stimulates yeast Sir2 deacetylase activity in vitro by alleviating the NAM inhibition. In this study, we determined that INAM stimulates Sir2 through an additional mechanism in vivo, which involves elevation of the intracellular NAD(+) concentration. INAM enhanced normal silencing at the rDNA locus but only partially suppressed the silencing defects of an npt1Δ mutant. Yeast cells grown in media lacking NA had a short replicative life span, which was extended by INAM in a SIR2-dependent manner and correlated with increased NAD(+). The INAM-induced increase in NAD(+) was strongly dependent on Pnc1 and Npt1, suggesting that INAM increases flux through the NAD(+) salvage pathway. Part of this effect was mediated by the NR salvage pathways, which generate NAM as a product and require Pnc1 to produce NAD(+). We also provide evidence suggesting that INAM influences the expression of multiple NAD(+) biosynthesis and salvage pathways to promote homeostasis during stationary phase.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.