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Cited by 63Cancer, Hypoxia, and MetabolismRedox biology and oxidative stressNitric Oxide and Endothelin Effects

The oxygen sensing signal cascade under the influence of reactive oxygen species

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Acker, Helmut·2005·Philosophical Transactions of the Royal Society B: Biological Sciences
DOI 10.1098/rstb.2005.1760PMC PMC1569600
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Abstract

Structural and functional integrity of organ function profoundly depends on a regular oxygen and glucose supply. Any disturbance of this supply becomes life threatening and may result in severe loss of organ function. Particular reductions in oxygen availability (hypoxia) caused by respiratory or blood circulation irregularities cannot be tolerated for longer periods due to an insufficient energy supply by anaerobic glycolysis. Complex cellular oxygen sensing systems have evolved to tightly regulate oxygen homeostasis. In response to variations in oxygen partial pressure (PO2), these systems induce adaptive and protective mechanisms to avoid or at least minimize tissue damage. These various responses might be based on a range of oxygen sensing signal cascades including an isoform of the neutrophil NADPH oxidase, different electron carrier units of the mitochondrial chain such as a specialized mitochondrial, low PO2 affinity cytochrome c oxidase (aa3) and a subfamily of 2-oxoglutarate dependent dioxygenases termed HIF (hypoxia inducible factor) prolyl-hydroxylase and HIF asparaginyl hydroxylase called factor-inhibiting HIF (FIH-1). Thus, specific oxygen sensing cascades involving reactive oxygen species as second messengers may by means of their different oxygen sensitivities, cell-specific and subcellular localization help to tailor various adaptive responses according to differences in tissue oxygen availability.

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  • Interventions that alter mitochondrial function, translation, or proteostasis may either suppress or enhance HIF signaling depending on the prevailing redox-oxygen context, a phenomenon not predictable from oxygen availability alone.

    “Interventions that alter mitochondrial function, translation, or proteostasis may either suppress or enhance HIF signaling depending on the prevailing redox–oxygen context, a phenomenon not predictable from oxygen availability alone.”

    From HIF inhibition: Current strategies and clinical challenges (2026) · cites this paper as [214]

    The ‘Reactive oxygen species’ section reports different HIF responses in normoxic and hypoxic redox settings and discusses mitochondrial ROS, supporting the claim that oxygen availability alone does not determine HIF signaling. The ‘Molecular mechanism’ section describes proteasomal degradation of HIF-1α, but our copy does not establish that interventions altering translation or proteostasis can each suppress or enhance HIF signaling depending on redox–oxygen context. No page numbers are available in the indexed passages. (LLM, conf=0.86)

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References 86 · Cited by 63

Research works printed but not linked: 45

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Authors
Acker, H.
Affiliations
University of Duisburg-Essen (DE)
Corresponding author
Acker, Helmut
ORCID
Acker, Helmut
Venue
Philosophical Transactions of the Royal Society B: Biological Sciences
Publisher
The Royal Society
Published
2005-11-03
Volume
360
Issue
1464
Pages
2201-2210
ISSN
  • 0962-8436 (ISSN-L)
  • 1471-2970
DOI
10.1098/rstb.2005.1760
PMC
PMC1569600
OpenAlex
W2002666678
Cited by
63
References
86
Citations by year
2026: 1 · 2025: 1 · 2022: 2 · 2021: 1 · 2020: 1 · 2019: 2 · 2018: 1 · 2017: 2 · 2016: 2 · 2015: 3 · 2014: 6 · 2013: 5 · 2012: 5
FWCI
2.09
Type
journal article
Language
en
Open access
Licence
royalsociety.org/journals/ethics-policies/data-sharing-mining/ (tdm)
Locations
  • Philosophical Transactions of the Royal Society B Biological Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
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 › Physiology › Nitric Oxide and Endothelin Effects
Keywords
oxygen sensing, reactive oxygen species, hypoxia, oxygen homeostasis, signaling pathways, NADPH oxidase, cytochrome c oxidase, mitochondrial electron transport chain, HIF prolyl hydroxylase, FIH-1, 2-oxoglutarate-dependent dioxygenase, oxygen partial pressure
MeSH terms
Adaptation, Physiological, Animals, Hypoxia, Carotid Body, Electron Transport Complex IV, Gene Expression Regulation, Homeostasis, Humans, Mixed Function Oxygenases, Oxygen, Partial Pressure, Repressor Proteins, Transcription Factors, Signal Transduction, Reactive Oxygen Species, NADPH Oxidases

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