ArticleMolecular and cellular biology2012
Hydrolase controls cellular NAD, sirtuin, and secondary metabolites.
Article in Molecular and cellular biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 46 citations in OpenAlex.
- Regulation of Histone Acetylation Modification on Biosynthesis of Secondary Metabolites in Fungi.International journal of molecular sciences · 2024Review
- Research Progress on the Mechanism and Function of Histone Acetylation Regulating the Interaction between Pathogenic Fungi and Plant Hosts.Journal of fungi (Basel, Switzerland) · 2024Review
- Sirtuin E deacetylase is required for full virulence of Aspergillus fumigatus.Communications biology · 2024Article
- The Histone Deacetylase HstD Regulates Fungal Growth, Development and Secondary Metabolite Biosynthesis inInternational journal of molecular sciences · 2023Article
- Systematic characterization ofFrontiers in microbiology · 2023Article
- Inactivation of MrSir2 in Monascus ruber Influenced the Developmental Process and the Production of Monascus Azaphilone Pigments.Applied biochemistry and biotechnology · 2022Article
- Post-translational modifications drive secondary metabolite biosynthesis in Aspergillus: a review.Environmental microbiology · 2022Review
- Potential antifungal targets based on histones post-translational modifications against invasive aspergillosis.Frontiers in microbiology · 2022Review
- Insights regarding sirtuin-dependent gene regulation during white koji production.Communicative & integrative biology · 2022Article
- On top of biosynthetic gene clusters: How epigenetic machinery influences secondary metabolism in fungi.Biotechnology advances · 2019Review
- Sirtuin E is a fungal global transcriptional regulator that determines the transition from the primary growth to the stationary phase.The Journal of biological chemistry · 2017Article
- The evolution of function within the Nudix homology clan.Proteins · 2017Article
- Novel β-1,4-Mannanase Belonging to a New Glycoside Hydrolase Family in Aspergillus nidulans.The Journal of biological chemistry · 2015Article
- The human NAD metabolome: Functions, metabolism and compartmentalization.Critical reviews in biochemistry and molecular biology · 2015Review
- A Nudix Hydrolase Protein, Ysa1, Regulates Oxidative Stress Response and Antifungal Drug Susceptibility in Cryptococcus neoformans.Mycobiology · 2014Article
- Fungus-specific sirtuin HstD coordinates secondary metabolism and development through control of LaeA.Eukaryotic cell · 2013Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cellular levels of NAD(+) and NADH are thought to be controlled by de novo and salvage mechanisms, although evidence has not yet indicated that they are regulated by NAD(+) degradation. Here we show that the conserved nudix hydrolase isozyme NdxA hydrolyzes and decreases cellular NAD(+) and NADH in Aspergillus nidulans. The NdxA-deficient fungus accumulated more NAD(+) during the stationary growth phase, indicating that NdxA maintains cellular NAD(+)/NADH homeostasis. The deficient strain also generated less of the secondary metabolites sterigmatocystin and penicillin G and of their gene transcripts than did the wild type. These defects were associated with a reduction in acetylated histone H4 on the gene promoters of aflR and ipnA that are involved in synthesizing secondary metabolites. Thus, NdxA increases acetylation levels of histone H4. We discovered that the novel fungal sirtuin isozyme SirA uses NAD(+) as a cosubstrate to deacetylate the lysine 16 residue of histone H4 on the gene promoter and represses gene expression. The impaired acetylation of histone and secondary metabolite synthesis in the NdxA-deficient strain were restored by eliminating functional SirA, indicating that SirA mediates NdxA-dependent regulation. These results indicated that NdxA controls total levels of NAD(+)/NADH and negatively regulates sirtuin function and chromatin structure.
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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.