ArticleThe EMBO journal2014
Regulation of G6PD acetylation by SIRT2 and KAT9 modulates NADPH homeostasis and cell survival during oxidative stress.
Article in The EMBO journal, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 174 papers.
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174 citing papers in PubMed, 264 citations in OpenAlex.
- Beyond biochemical cascades: the biophysical execution of disulfidptosis via actin network collapse.Molecular biology reports · 2026Review
- SUMOylation-stabilized G6PD orchestrates metabolic rewiring for oxidative stress survival and chemoresistance in HCC via a PKCδ-phosphorylation trigger.Cell death and differentiation · 2026Article
- Pentose Phosphate Pathway Is Critical for Providing Energy by Bypassing 6-Phosphofructo-1-Kinase (PFK1) During Increased Neuronal Activity.Metabolites · 2026Review
- Lactylation and acetylation: parallel paths, divergent deeds, and research dilemmas.Journal of translational medicine · 2026Review
- MTHFD2 modulates neural stem cell proliferation and apoptosis after intracerebral hemorrhage by regulating mitochondrial NADPH homeostasis.Journal of translational medicine · 2026Article
- TIGAR regulates intestinal mucus barrier integrity by inhibiting lactylation of G6PD/6PGD in ulcerative colitis.Nature communications · 2026Article
- OGT Silencing Protects against Trophoblast Ferroptosis in Gestational Diabetes Mellitus Via ELP3 O-GlcNAcylation Suppression.Applied biochemistry and biotechnology · 2026Article
- Article
- Photo/Biohybrid Catalytic System for Application in Semiartificial Photosynthesis of COChemical reviews · 2026Review
- The role of metabolic reprogramming in oocyte development: research progress and prospects.Frontiers in reproductive health · 2026Review
- Characterization of lactylation-related subtypes and diagnostic markers in myocardial ischemic reperfusion injury using weighted gene coexpression network analysis and machine learning.Frontiers in immunology · 2026Article
- Acetylation modification in malignant progression and therapeutic resistance of gliomas.Frontiers in cell and developmental biology · 2026Review
- The research progress on the role of glucose-6-phosphate dehydrogenase in immune regulation.PeerJ · 2026Review
- The Yin-Yang balance of SIRT1 and SIRT2 in cancer metabolic remodeling.International journal of biological sciences · 2026Review
- Protein acetylation in atherosclerosis: beyond inflammation to core cellular processes and therapeutic potential.Frontiers in immunology · 2026Review
- Genome-wide association study revealed genomic regions associated with tuber quality traits in water yam (Dioscorea alata L.).PloS one · 2026Article
- Keeping up with the nicotinamides: NADP(H), the forgotten circadian cofactor that keeps metabolic time.Life metabolism · 2025Review
- Effects of aging and anti-aging dietary restriction on regulators of the [NADPH]/[NADPFree radical biology & medicine · 2025Review
- Elevating cytosolic NADPH metabolism in endothelial cells ameliorates vascular aging.Nature communications · 2025Article
- Growth Phase-Dependent Changes in the Carbohydrate Metabolism of Penicillium Strains from Diverse Temperature Classes in Response to Cold Stress.International journal of molecular sciences · 2025Article
114 more citing papers are in PubMed but not listed here.
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15 authors at 5 institutions in 2 countries.
Funding
Abstract
Glucose-6-phosphate dehydrogenase (G6PD) is a key enzyme in the pentose phosphate pathway (PPP) and plays an essential role in the oxidative stress response by producing NADPH, the main intracellular reductant. G6PD deficiency is the most common human enzyme defect, affecting more than 400 million people worldwide. Here, we show that G6PD is negatively regulated by acetylation on lysine 403 (K403), an evolutionarily conserved residue. The K403 acetylated G6PD is incapable of forming active dimers and displays a complete loss of activity. Knockdown of G6PD sensitizes cells to oxidative stress, and re-expression of wild-type G6PD, but not the K403 acetylation mimetic mutant, rescues cells from oxidative injury. Moreover, we show that cells sense extracellular oxidative stimuli to decrease G6PD acetylation in a SIRT2-dependent manner. The SIRT2-mediated deacetylation and activation of G6PD stimulates PPP to supply cytosolic NADPH to counteract oxidative damage and protect mouse erythrocytes. We also identified KAT9/ELP3 as a potential acetyltransferase of G6PD. Our study uncovers a previously unknown mechanism by which acetylation negatively regulates G6PD activity to maintain cellular NADPH homeostasis during oxidative stress.
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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.