ArticleNature communications2015
D2HGDH regulates alpha-ketoglutarate levels and dioxygenase function by modulating IDH2.
Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 88 citations in OpenAlex.
- Tuning epigenetics to enhance cancer virotherapy.Acta pharmaceutica Sinica. B · 2026Review
- Gestational exposure to PMJournal of advanced research · 2026Article
- Excitatory amino acid transporters support mast cell degranulation via α-KG-mediated methylation of Spp1.Cellular & molecular immunology · 2026Article
- 2-Hydroxyglutarate in onco-pathway: a metabolic driver of proto-oncogene activation.Frontiers in oncology · 2026Review
- Substitution of ZnACS omega · 2025Article
- α-Ketoglutarate promotes amino acid depletion and suppresses B-cell lymphoma growth and development.Blood · 2025Article
- Stereochemistry and Charged State Influence Effector Outcomes of d-2-Hydroxyglutarate Dehydrogenase Ligands.Biochemistry · 2025Article
- Intrauterine hyperglycemia impairs mouse primordial germ cell development and fertility by sex-specific epigenetic reprogramming interference.Cell discovery · 2025Article
- New alleles of D-2-hydroxyglutarate dehydrogenase enable studies of oncometabolite function in Drosophila melanogaster.G3 (Bethesda, Md.) · 2025Article
- D2HGDH Deficiency Regulates Seizures through GSH/Prdx6/ROS-Mediated Excitatory Synaptic Activity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Epigenetic and metabolic reprogramming via nanotechnology: a synergistic approach to cancer vaccination in lung tumors.Frontiers in genetics · 2025Review
- IRF8-mutant B cell lymphoma evades immunity through a CD74-dependent deregulation of antigen processing and presentation in MHCII complexes.Science advances · 2024Article
- Prenatal 1-Nitropyrene Exposure Causes Autism-Like Behavior Partially by Altering DNA Hydroxymethylation in Developing Brain.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Insights into the role of RNA mGenes & diseases · 2024Review
- Metabolic basis of cardiac dysfunction in cancer patients.Current opinion in cardiology · 2024Review
- Epigenetic modulators link mitochondrial redox homeostasis to cardiac function in a sex-dependent manner.Nature communications · 2024Article
- Copy Number Variation Regions Differing in Segregation Patterns Span Different Sets of Genes.Animals : an open access journal from MDPI · 2023Article
- α-KG inhibits tumor growth of diffuse large B-cell lymphoma by inducing ROS and TP53-mediated ferroptosis.Cell death discovery · 2023Article
- Metabolic Reprogramming and Potential Therapeutic Targets in Lymphoma.International journal of molecular sciences · 2023Review
- Metabolic determinants of tumour initiation.Nature reviews. Endocrinology · 2023Review
3 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
22 authors at 4 institutions in 2 countries.
Funding
Abstract
Isocitrate dehydrogenases (IDH) convert isocitrate to alpha-ketoglutarate (α-KG). In cancer, mutant IDH1/2 reduces α-KG to D2-hydroxyglutarate (D2-HG) disrupting α-KG-dependent dioxygenases. However, the physiological relevance of controlling the interconversion of D2-HG into α-KG, mediated by D2-hydroxyglutarate dehydrogenase (D2HGDH), remains obscure. Here we show that wild-type D2HGDH elevates α-KG levels, influencing histone and DNA methylation, and HIF1α hydroxylation. Conversely, the D2HGDH mutants that we find in diffuse large B-cell lymphoma are enzymatically inert. D2-HG is a low-abundance metabolite, but we show that it can meaningfully elevate α-KG levels by positively modulating mitochondrial IDH activity and inducing IDH2 expression. Accordingly, genetic depletion of IDH2 abrogates D2HGDH effects, whereas ectopic IDH2 rescues D2HGDH-deficient cells. Our data link D2HGDH to cancer and describe an additional role for the enzyme: the regulation of IDH2 activity and α-KG-mediated epigenetic remodelling. These data further expose the intricacies of mitochondrial metabolism and inform on the pathogenesis of D2HGDH-deficient diseases.
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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.