The DOI matches its Crossref record; 233 of the 233 references it cites were found in a registry or an index.
Cellular adaptation to hypoxia through hypoxia inducible factors and beyond
Open accessAbstract
Molecular oxygen (O 2) sustains intracellular bioenergetics and is consumed by numerous biochemical reactions, making it essential for most species on Earth. Accordingly, decreased oxygen concentration (hypoxia) is a major stressor that generally subverts life of aerobic species and is a prominent feature of pathological states encountered in bacterial infection, inflammation, wounds, cardiovascular defects and cancer. Therefore, key adaptive mechanisms to cope with hypoxia have evolved in mammals. Systemically, these adaptations include increased ventilation, cardiac output, blood vessel growth and circulating red blood cell numbers. On a cellular level, ATP-consuming reactions are suppressed, and metabolism is altered until oxygen homeostasis is restored. A critical question is how mammalian cells sense oxygen levels to coordinate diverse biological outputs during hypoxia. The best-studied mechanism of response to hypoxia involves hypoxia inducible factors (HIFs), which are stabilized by low oxygen availability and control the expression of a multitude of genes, including those involved in cell survival, angiogenesis, glycolysis and invasion/metastasis. Importantly, changes in oxygen can also be sensed via other stress pathways as well as changes in metabolite levels and the generation of reactive oxygen species by mitochondria. Collectively, this leads to cellular adaptations of protein synthesis, energy metabolism, mitochondrial respiration, lipid and carbon metabolism as well as nutrient acquisition. These mechanisms are integral inputs into fine-tuning the responses to hypoxic stress.
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“Cancer hypoxia and the induced adaptation mechanisms are two of the major causes of therapy resistance.”
From Hypoxia Signaling in Cancer: From Basics to Clinical Practice (2021) · cites this paper as [5]
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“However, chronic hypoxia is the most typical form of hypoxia in tumor tissues [5].”
From Hypoxia Signaling in Cancer: From Basics to Clinical Practice (2021) · cites this paper as [5]
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Metadata
- Authors
- Lee, P., Chandel, N. S., & Simon, M. C.
- Affiliations
- University of Pennsylvania (US)
- Northwestern University (US)
- Corresponding author
- Lee, Pearl
- Chandel, Navdeep S.
- Simon, M. Celeste
- Venue
- Nature Reviews Molecular Cell Biology
- Published
- 2020-03-06
- Volume
- 21
- Issue
- 5
- Pages
- 268-283
- ISSN
- 1471-0072 (ISSN-L)
- 1471-0080
- PMC
- PMC7222024
- OpenAlex
- W3009721059
- Cited by
- 1,272
- References
- 233
- Citations by year
- 2026: 207 · 2025: 275 · 2024: 209 · 2023: 201 · 2022: 186 · 2021: 137 · 2020: 55
- FWCI
- 14.94
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Reviews Molecular Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (F32CA217185, P01CA104838, R35CA197532, R01CA158301, R35CA220483)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (T32AR053461)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
- Keywords
- hypoxia, hypoxia-inducible factor, cellular adaptation, oxygen sensing, energy metabolism, glycolysis, angiogenesis, reactive oxygen species, mitochondrial respiration, nutrient uptake, protein synthesis, cancer, cardiovascular disease, inflammation, wound healing, transcriptional response
- MeSH terms
- Adenosine Triphosphate, Energy Metabolism, Humans, Mitochondria, Oxygen, Signal Transduction, Cell Hypoxia, Reactive Oxygen Species, Oxidative Stress
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