ArticleNature metabolism2025
An alternative route for β-hydroxybutyrate metabolism supports cytosolic acetyl-CoA synthesis in cancer cells.
Article in Nature metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Ketogenic Diet as an Adjuvant in Epithelial Cancers: Mechanisms, Model Systems, and Translational Opportunities.Cancers · 2026Review
- A β-Hydroxybutyrylation-FOXM1/CENPA Axis Links Ketone-Body Metabolism to Mitotic Transcription in Basal-like Breast Cancer.International journal of molecular sciences · 2026Article
- Reverse cardio-oncology: neuroendocrine axis activation and cardiovascular-disease-derived factors synergistically remodel the tumor microenvironment.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- A Stable Isotope Tracing Primer for the Mass Spectrometrist.Annual review of analytical chemistry (Palo Alto, Calif.) · 2026Review
- The Influence of Basic Therapy and New Drugs on NO-Dependent Mechanisms of Cardiac Destruction in Chronic Heart Failure.Biomedicines · 2026Review
- Identification of pyroptosis and hypoxia related molecular subtypes and a prognostic signature in colorectal cancer.Discover oncology · 2026Article
- Adaptation to glucose restriction and β-hydroxybutyrate supplementation is associated with metabolic flexibility in lung cancer cells.Scientific reports · 2026Article
- Review
- Association between ketone body levels and chronic liver disease: Epidemiological studies and potential mechanisms.AIMS public health · 2026Review
- Ketogenic diet prevents obesity-associated pancreatic cancer independent of weight loss and induces pancreatic metabolic reprogramming.bioRxiv : the preprint server for biology · 2025Article
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14 authors.
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Abstract
Cancer cells are exposed to diverse metabolites in the tumour microenvironment that are used to support the synthesis of nucleotides, amino acids and lipids needed for rapid cell proliferation. In some tumours, ketone bodies such as β-hydroxybutyrate (β-OHB), which are elevated in circulation under fasting conditions or low glycemic diets, can serve as an alternative fuel that is metabolized in the mitochondria to provide acetyl-CoA for the tricarboxylic acid (TCA) cycle. Here we identify a non-canonical route for β-OHB metabolism that bypasses the TCA cycle to generate cytosolic acetyl-CoA. We show that in cancer cells that can metabolize ketones, β-OHB-derived acetoacetate in the mitochondria can be shunted into the cytosol, where acetoacetyl-CoA synthetase (AACS) and thiolase convert it into cytosolic acetyl-CoA. This alternative metabolic routing allows β-OHB to avoid oxidation in the mitochondria and to be used as a major source of cytosolic acetyl-CoA, even when other key cytosolic acetyl-CoA precursors such as glucose are available in excess. Finally, we demonstrate that ketone body metabolism, including this alternative AACS-dependent route, can support the growth of mouse Kras
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