Metabolic coordination of cell fate by α-ketoglutarate-dependent dioxygenases
Open accessAbstract
Cell fate determination requires faithful execution of gene expression programs, which are increasingly recognized to respond to metabolic inputs. In particular, the family of α-ketoglutarate (αKG)-dependent dioxygenases, which include several chromatin-modifying enzymes, are emerging as key mediators of metabolic control of cell fate. αKG-dependent dioxygenases consume the metabolite αKG (also known as 2-oxoglutarate) as an obligate cosubstrate and are inhibited by succinate, fumarate, and 2-hydroxyglutarate. Here, we review the role of these metabolites in the control of dioxygenase activity and cell fate programs. We discuss the biochemical and transcriptional mechanisms enabling these metabolites to control cell fate and review evidence that nutrient availability shapes tissue-specific fate programs via αKG-dependent dioxygenases.
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αKG-dependent dioxygenases require αKG, ferrous iron, and oxygen as cosubstrates and are inhibited by high levels of succinate and fumarate.
“These enzymes all require αKG, ferrous iron, and oxygen as cosubstrates and are inhibited by high levels of succinate and fumarate (161), thereby integrating multiple metabolic pathways in the control of gene expression programs and, ultimately, cell fate decisions.”
From Regulation and function of the mammalian tricarboxylic acid cycle (2023) · cites this paper as [161]
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References 90 · Cited by 165
- Authors
- Baksh, S. C., & Finley, L. W. S.
- Affiliations
- Howard Hughes Medical Institute (US)
- Memorial Sloan Kettering Cancer Center (US)
- Corresponding author
- Finley, Lydia W.S.
- Venue
- Trends in Cell Biology
- Publisher
- Elsevier BV
- Published
- 2021-01
- Volume
- 31
- Issue
- 1
- Pages
- 24-36
- ISSN
- 0962-8924 (ISSN-L)
- PMC
- PMC7748998
- OpenAlex
- W3094521060
- Cited by
- 165
- References
- 90
- Citations by year
- 2026: 50 · 2025: 32 · 2024: 27 · 2023: 23 · 2022: 22 · 2021: 11
- FWCI
- 1.36
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Trends in Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Starr Foundation
- Edward Mallinckrodt, Jr. Foundation
- National Cancer Institute
- Concern Foundation
- Searle Scholars Program
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Keywords
- alpha-ketoglutarate-dependent dioxygenase, alpha-ketoglutarate, cell fate determination, metabolic regulation of gene expression, chromatin-modifying enzymes, 2-hydroxyglutarate, nutrient availability, transcriptional regulation
- MeSH terms
- Alpha-Ketoglutarate-Dependent Dioxygenase FTO, Animals, Enhancer Elements, Genetic, Humans, Mutation, Neoplasms, Transcription Factors, Cell Lineage
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