ArticleNature metabolism2021
NADPH levels affect cellular epigenetic state by inhibiting HDAC3-Ncor complex.
Article in Nature metabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 71 citations in OpenAlex.
- Increasing cytosolic NADPH to mimic exercise.Nature metabolism · 2026Article
- NADPH oxidases in immunometabolism and disease pathology: mechanistic networks, pollutant triggers, and therapeutic frontiers.Cellular & molecular immunology · 2026Review
- Pentose phosphate pathway-derived NADPH facilitates physiological hypertrophy and alleviates ischemia-reperfusion injury in the heart.Nature metabolism · 2026Article
- Post-translational modifications in metabolic reprogramming: implications for metabolic therapy and immunotherapy in cancer.Signal transduction and targeted therapy · 2026Review
- Kinsenoside Targets IDH1 to Restore Microglial Immune-Metabolic Homeostasis for Alzheimer's Disease Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- NADPH Dehydrogenase Gene Regulates Energy Distribution and Fatty Acid Metabolism During Fruiting Body Formation in the Filamentous Fungus Podospora anserina.Microbial biotechnology · 2026Article
- Mitochondrial NADK2-dependent NADPH controls tau oligomer uptake in human neurons.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Metabolic oxidoreductases: central regulators of the epigenetic landscapes in stemness.Experimental & molecular medicine · 2026Review
- Hypothalamic malate dehydrogenase 2 modulates systemic glucose metabolism through oxytocin-mediated thermogenesis.Cell reports. Medicine · 2026Article
- NADPH acts as an endogenous P2X7 receptor modulator to gate neuroinflammatory responses of microglia.Acta pharmacologica Sinica · 2026Article
- The role of metabolic reprogramming in oocyte development: research progress and prospects.Frontiers in reproductive health · 2026Review
- Long non-coding RNA LINC01532 sustains redox homeostasis and accelerates lenvatinib resistance in hepatocellular carcinoma.Journal of advanced research · 2025Article
- Metabolic-Electrophysiological Coupling in Heart Failure: from Bidirectional Decoupling to Therapeutic Recoupling.Current heart failure reports · 2025Review
- Elevating cytosolic NADPH metabolism in endothelial cells ameliorates vascular aging.Nature communications · 2025Article
- Melatonin Modulates Glucose Metabolism Reprogramming via Targeting G6PD to Alleviate Lead-Induced Hepatocytes Pyroptosis in Common Carp (Cyprinus carpio L.).Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Immunometabolism: crosstalk with tumor metabolism and implications for cancer immunotherapy.Molecular cancer · 2025Review
- PHGDH-mediated serine synthesis in astrocytes supports neuroinflammation by sustaining NADH level to promote histone acetylation.Cell death & disease · 2025Article
- ACAT1-Mediated ME2 Acetylation Drives Chemoresistance in Ovarian Cancer by Linking Glutaminolysis to Lactate Production.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Xenotopic synthetic biology: Prospective tools for delaying aging and age-related diseases.Science advances · 2025Review
- The metabolic significance of peripheral tissue clocks.Communications biology · 2025Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
NADPH has long been recognized as a key cofactor for antioxidant defence and reductive biosynthesis. Here we report a metabolism-independent function of NADPH in modulating epigenetic status and transcription. We find that the reduction of cellular NADPH levels, achieved by silencing malic enzyme or glucose-6-phosphate dehydrogenase, impairs global histone acetylation and transcription in both adipocytes and tumour cells. These effects can be reversed by supplementation with exogenous NADPH or by inhibition of histone deacetylase 3 (HDAC3). Mechanistically, NADPH directly interacts with HDAC3 and interrupts the association between HDAC3 and its co-activator nuclear receptor corepressor 2 (Ncor2; SMRT) or Ncor1, thereby impairing HDAC3 activation. Interestingly, NADPH and the inositol tetraphosphate molecule Ins(1,4,5,6)P
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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.