Surviving hypoxia by modulation of mRNA translation rate
Open accessAbstract
Oxygen in eukaryotic metabolism Oxygen consumption of tissues and processes Metabolic rate depression mRNA translation in hypoxia: the down and up and down Regulation of global mRNA translation in hypoxia Regulation of specific mRNA translation in hypoxia Can an alteration of the translational machinery cause a specific change in gene expression? Cells can survive hypoxia/anoxia by metabolic rate depression, which involves lowering of mRNA translation rates in an ATP‐dependent manner. By activating anaerobic ATP production (glycolysis), the inhibitory influence on mRNA translation in hypoxia can be abolished. In severe hypoxia, glycolysis cannot fully restore the ATP demand, thus causing a long‐lasting inhibition of global protein synthesis. During moderate hypoxia, fermentative ATP production may maintain normal ATP levels. However, an activation of hypoxia tolerance mechanisms, including specific mRNA translation, also takes place. The latter may be attributed to oxygen‐dependent (but not ATP dependent) processes such as the activation of the hypoxia‐inducible factor cascade. In summary, hypoxia‐induced decline in cellular ATP level can be counteracted by suppression of global mRNA translation rate. Sustained protein synthesis seems to be attributed to the activation of specific mRNA translation under long‐term hypoxic conditions.
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There are two principal mechanisms that operate in response to hypoxia: a rapid response involving phosphorylation of eIF2α through PERK and the UPR, and a longer term response dependent on suppression of the mTOR pathway.
“There are two principal mechanisms that operate, a rapid response involving phosphorylation of eIF2α through PERK and the UPR, and a longer term response dependent on suppression of the mTOR pathway (181, 585).”
From Placental Origins of Chronic Disease (2016) · cites this paper as [181]
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- Authors
- Fähling, M.
- Affiliations
- Charité – Universitätsmedizin Berlin (DE)
- Corresponding author
- Fähling, Michael
- ORCID
- Fähling, Michael
- Venue
- Journal of Cellular and Molecular Medicine
- Publisher
- Wiley
- Published
- 2009-09
- Volume
- 13
- Issue
- 9a
- Pages
- 2770-2779
- ISSN
- 1582-1838 (ISSN-L)
- 1582-4934
- PMC
- PMC4498934
- OpenAlex
- W2008844725
- Cited by
- 54
- References
- 114
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 2 · 2023: 3 · 2022: 6 · 2020: 3 · 2019: 4 · 2018: 5 · 2017: 6 · 2016: 6 · 2015: 3 · 2014: 4 · 2013: 5 · 2012: 1
- FWCI
- 0.08
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Cellular and Molecular Medicine (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (845/2-1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Keywords
- hypoxia, mRNA translation, translational regulation, metabolic depression, glycolysis, ATP production, hypoxia-inducible factor, protein synthesis, oxygen consumption, anoxia tolerance, gene expression regulation
- MeSH terms
- Animals, Cell Survival, Gene Expression Regulation, Humans, Oxygen Consumption, RNA, Messenger, Protein Biosynthesis, Cell Hypoxia
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