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Cited by 220Nitric Oxide and Endothelin EffectsMitochondrial Function and PathologyRedox biology and oxidative stress

Nitric Oxide, Cytochrome C Oxidase, and the Cellular Response to Hypoxia

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Taylor, Cormac T., Moncada, Salvador·2010·Arteriosclerosis, Thrombosis, and Vascular Biology
DOI 10.1161/atvbaha.108.181628
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Abstract

Cytochrome c oxidase (CcO; complex IV of the mitochondrial electron transport chain) is the primary site of cellular oxygen consumption and, as such, is central to oxidative phosphorylation and the generation of adenosine-triphosphate. Nitric oxide (NO), an endogenously-generated gas, modulates the activity of CcO. Depending on the intracellular oxygen concentration and the resultant dominant redox state of CcO, the interaction between CcO and NO can have a range of signaling consequences for cells in the perception of changes in oxygen concentration and the initiation of adaptive responses. At higher oxygen concentrations, when CcO is predominantly in an oxidized state, it consumes NO. At lower oxygen concentrations, when CcO is predominantly reduced, NO is not consumed and accumulates in the microenvironment, with implications for both the respiratory rate of cells and the local vascular tone. Changes in the availability of intracellular oxygen and in the generation of reactive oxygen species that accompany these interactions result in cell signaling and in regulation of oxygen-sensitive pathways that ultimately determine the nature of the cellular response to hypoxia.

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  • In competition with oxygen, nitric oxide binds to cytochrome c oxidase in the mitochondrial electron transport chain, leading to inhibition of mitochondrial respiration.

    “In competition with oxygen, nitric oxide binds to cytochrome c oxidase in the mitochondrial electron transport chain, which leads to inhibition of mitochondrial respiration.[93][94][95]”

    From Nitrate-Nitrite-Nitric Oxide Pathway: Implications for Anesthesiology and Intensive Care (2010) · cites this paper as [95]

    The ‘Interaction Between Nitric Oxide and Cytochrome C Oxidase’ section says NO binds to reduced cytochrome c oxidase in competition with oxygen and can inhibit respiration. But the claim omits two limits: binding to the oxidized enzyme is not competitive with oxygen, and initial enzyme inhibition does not reduce oxygen consumption; respiration falls only as NO increases or oxygen decreases. No page number is available in our copy. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Taylor, C. T., & Moncada, S.
Affiliations
University College Dublin (IE)
ORCID
Venue
Arteriosclerosis, Thrombosis, and Vascular Biology
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2010-04
Volume
30
Issue
4
Pages
643-647
ISSN
  • 1079-5642 (ISSN-L)
  • 1524-4636
DOI
10.1161/atvbaha.108.181628
OpenAlex
W2073210360
Cited by
220
References
10
Citations by year
2026: 8 · 2025: 9 · 2024: 12 · 2023: 10 · 2022: 14 · 2021: 12 · 2020: 12 · 2019: 10 · 2018: 8 · 2017: 8 · 2016: 9 · 2015: 18 · 2014: 13 · 2013: 14 · 2012: 24
FWCI
2.32
Type
journal article
Language
en
Open access
Locations
  • Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
  • PubMed (publishedVersion)
  • Research Explorer (The University of Manchester) (submittedVersion)
  • UCL Discovery (University College London) (submittedVersion)
Topics
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
Keywords
nitric oxide, cytochrome c oxidase, hypoxia, mitochondrial electron transport chain, oxygen sensing, redox state, oxidative phosphorylation, reactive oxygen species, signal transduction, vascular tone, oxygen consumption
MeSH terms
Animals, Blood Vessels, Electron Transport Complex IV, Homeostasis, Humans, Mitochondria, Nitric Oxide, Oxidation-Reduction, Oxygen, Signal Transduction, Cell Hypoxia, Reactive Oxygen Species, Hypoxia-Inducible Factor 1, alpha Subunit

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