Cited by 303Cancer, Lipids, and MetabolismCancer, Hypoxia, and MetabolismMetabolism, Diabetes, and Cancer

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Acetyl-CoA metabolism in cancer

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Guertin, David A., Wellen, Kathryn E.·2023·Nature Reviews Cancer

DOI 10.1038/s41568-022-00543-5PMC PMC11137663

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Abstract

Few metabolites can claim a more central and versatile role in cell metabolism than acetyl coenzyme A (acetyl-CoA). Acetyl-CoA is produced during nutrient catabolism to fuel the tricarboxylic acid cycle and is the essential building block for fatty acid and isoprenoid biosynthesis. It also functions as a signalling metabolite as the substrate for lysine acetylation reactions, enabling the modulation of protein functions in response to acetyl-CoA availability. Recent years have seen exciting advances in our understanding of acetyl-CoA metabolism in normal physiology and in cancer, buoyed by new mouse models, in vivo stable-isotope tracing approaches and improved methods for measuring acetyl-CoA, including in specific subcellular compartments. Efforts to target acetyl-CoA metabolic enzymes are also advancing, with one therapeutic agent targeting acetyl-CoA synthesis receiving approval from the US Food and Drug Administration. In this Review, we give an overview of the regulation and cancer relevance of major metabolic pathways in which acetyl-CoA participates. We further discuss recent advances in understanding acetyl-CoA metabolism in normal tissues and tumours and the potential for targeting these pathways therapeutically. We conclude with a commentary on emerging nodes of acetyl-CoA metabolism that may impact cancer biology. Acetyl coenzyme A (acetyl-CoA) is a key metabolite in carbohydrate and lipid metabolism and plays a role in signalling through protein acetylation, and the dysregulation of these pathways is a hallmark of various cancers. In this Review, Guertin and Wellen give an overview of acetyl-CoA metabolism in health and in cancer and discuss emerging therapeutic strategies for targeting metabolic pathways involving acetyl-CoA.

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Authors: Guertin, D. A., & Wellen, K. E.
Affiliations: University of Massachusetts Chan Medical School (US)
University of Pennsylvania (US)
Corresponding author: Guertin, David A.
Wellen, Kathryn E.
ORCID: Guertin, David A.
Wellen, Kathryn E.
Venue: Nature Reviews Cancer
Publisher: Springer Science and Business Media LLC
Published: 2023-01-19
Volume: 23
Issue: 3
Pages: 156-172
ISSN: 1474-175X (ISSN-L)
1474-1768
DOI: 10.1038/s41568-022-00543-5
PMC: PMC11137663
OpenAlex: W4317436153
Cited by: 303
References: 200
Citations by year: 2026: 85 · 2025: 120 · 2024: 69 · 2023: 29
FWCI: 9.57
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.springernature.com/gp/researchers/text-and-data-mining (tdm)
www.springernature.com/gp/researchers/text-and-data-mining (vor)
Locations: Nature reviews. Cancer (publishedVersion, cc-by)
PubMed (publishedVersion)
PubMed Central (acceptedVersion, cc-by)
Funders: National Institutes of Health
National Cancer Institute (R01CA174761, R01CA248315, R01CA228339, R01CA262055)
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK094004, R01DK116005, R01DK127175)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Keywords: acetyl-CoA metabolism, cancer metabolism, TCA cycle, fatty acid synthesis, isoprenoid biosynthesis, lysine acetylation, protein acetylation, metabolic signalling, stable isotope tracing
MeSH terms: Acetyl Coenzyme A, Animals, Disease Models, Animal, Humans, Neoplasms, Mice, Metabolic Networks and Pathways

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