ArticleProceedings of the National Academy of Sciences of the United States of America2016
Oncometabolite d-2-hydroxyglutarate impairs α-ketoglutarate dehydrogenase and contractile function in rodent heart.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers.
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Who cites it
98 citing papers in PubMed, 137 citations in OpenAlex.
- Trial
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- Cardiac Modulation byCurrent issues in molecular biology · 2026Article
- Targeting immunometabolic pathways with AZD1656 alleviates inflammation and metabolic dysfunction in type 2 diabetic cardiomyopathy.Nature cardiovascular research · 2026Article
- Metabo-epigenetic circuits of heart failure: chromatin-modifying enzymes as determinants of metabolic plasticity.EMBO molecular medicine · 2026Review
- Metabolomics-constrained modelling reveals dominant oxidative metabolism in the Egyptian fruit bat myocardium.PloS one · 2026Article
- Multi-trait association analysis reveals shared genetic architecture between lung cancer and cardiometabolic diseases.iScience · 2025Article
- Wnt/β-catenin signaling regulates cardiac Cx43 in a metabolic substrate-dependent manner.Journal of molecular and cellular cardiology plus · 2025Article
- Bat power-metabolic profiling of the Egyptian fruit batbioRxiv : the preprint server for biology · 2025Article
- Cardiac intermediary metabolism in heart failure: substrate use, signalling roles and therapeutic targets.Nature reviews. Cardiology · 2025Review
- Interferon gamma signaling drives cardiac metabolic rewiring.bioRxiv : the preprint server for biology · 2025Article
- Insights Into Heart-Tumor Interactions in Heart Failure.Circulation research · 2025Review
- Exosomal transfer of pro-pyroptotic miR-216a-5p exacerbates anthracycline cardiotoxicity through breast cancer-heart pathological crosstalk.Signal transduction and targeted therapy · 2025Article
- Changes in tumor and cardiac metabolism upon immune checkpoint.Basic research in cardiology · 2025Review
- Cardiac wasting in patients with cancer.Basic research in cardiology · 2025Review
- Identification of signature genes and subtypes for heart failure diagnosis based on machine learning.Frontiers in cardiovascular medicine · 2025Article
- Article
- Cancer metabolism rewiring and chromatin methylation: a vulnerable epi-metabolic link.Frontiers in epigenetics and epigenomics · 2025Article
38 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Hematologic malignancies are frequently associated with cardiac pathologies. Mutations of isocitrate dehydrogenase 1 and 2 (IDH1/2) occur in a subset of acute myeloid leukemia patients, causing metabolic and epigenetic derangements. We have now discovered that altered metabolism in leukemic cells has a profound effect on cardiac metabolism. Combining mathematical modeling and in vivo as well as ex vivo studies, we found that increased amounts of the oncometabolite d-2-hydroxyglutarate (D2-HG), produced by IDH2 mutant leukemic cells, cause contractile dysfunction in the heart. This contractile dysfunction is associated with impaired oxidative decarboxylation of α-ketoglutarate, a redirection of Krebs cycle intermediates, and increased ATP citrate lyase (ACL) activity. Increased availability of D2-HG also leads to altered histone methylation and acetylation in the heart. We propose that D2-HG promotes cardiac dysfunction by impairing α-ketoglutarate dehydrogenase and induces histone modifications in an ACL-dependent manner. Collectively, our results highlight the impact of cancer cell metabolism on function and metabolism of the heart.
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