Mitochondria and Hypoxia: Metabolic Crosstalk in Cell-Fate Decisions
Open accessAbstract
Alterations in mitochondrial metabolism influence cell differentiation and growth. This process is regulated by the activity of 2-oxoglutarate (2OG)-dependent dioxygenases (2OGDDs) - a diverse superfamily of oxygen-consuming enzymes - through modulation of the epigenetic landscape and transcriptional responses. Recent reports have described the role of mitochondrial metabolites in directing 2OGDD-driven cell-fate switches in stem cells (SCs), immune cells, and cancer cells. An understanding of the metabolic mechanisms underlying 2OGDD autoregulation is required for therapeutic targeting of this system. We propose a model dependent on oxygen and metabolite availability and discuss how this integrates 2OGDD metabolic signalling, the hypoxic transcriptional response, and fate-determining epigenetic changes.
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When hypoxia is prolonged or adaptive capacity is exceeded, failure to restore oxygen homeostasis triggers programmed cell death pathways.
“When hypoxia is prolonged or adaptive capacity is exceeded, the failure to restore oxygen homeostasis triggers programmed cell death pathways”
From HIF inhibition: Current strategies and clinical challenges (2026) · cites this paper as [6]
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Regulation of the HIF switch in human endothelial and cancer cells
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HIF inhibition: Current strategies and clinical challenges
Więch-Walów, A., Bartoszewska, S., Barton, A., Czechowicz, P., Dudzik, J., Wielockx, B., Collawn, J. F., & Bartoszewski, R. (2026) · Redox biology · doi:10.1016/j.redox.2026.104220 · Cited by 3 · see citing works
“When hypoxia is prolonged or adaptive capacity is exceeded, the failure to restore oxygen homeostasis triggers programmed cell death pathways [6,13,14].”
- Authors
- Bargiela, D., Burr, S. P., & Chinnery, P. F.
- Affiliations
- University of Cambridge (GB)
- Corresponding author
- Chinnery, Patrick F.
- Venue
- Trends in Endocrinology & Metabolism
- Publisher
- Elsevier BV
- Published
- 2018-04
- Volume
- 29
- Issue
- 4
- Pages
- 249-259
- ISSN
- 1043-2760 (ISSN-L)
- OpenAlex
- W2790931190
- Cited by
- 60
- References
- 28
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 7 · 2023: 7 · 2022: 8 · 2021: 9 · 2020: 10 · 2019: 8 · 2018: 2
- FWCI
- 0.75
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- Trends in Endocrinology and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Apollo (University of Cambridge) (submittedVersion)
- Apollo
- Funders
- Wellcome Trust (101876/Z/13/Z)
- Medical Research Council Mitochondrial Biology Unit (MC_UP_1501/2)
- Medical Research Council (UK) Centre for Translational Muscle Disease (G0601943)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Physical Sciences › Chemistry › Inorganic Chemistry › Metal-Catalyzed Oxygenation Mechanisms
- Keywords
- mitochondria, hypoxia, 2-oxoglutarate-dependent dioxygenase, cell fate determination, mitochondrial metabolism, epigenetic regulation, stem cells, immune cells, cancer cells, metabolic signalling, oxygen availability
- MeSH terms
- Animals, Hypoxia, Cell Differentiation, Homeostasis, Humans, Mitochondria
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