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Reversible inhibition of cytochrome c oxidase, the terminal enzyme of the mitochondrial respiratory chain, by nitric oxide: Implications for neurodegenerative diseases
Abstract
Incubation of rat skeletal muscle mitochondria with the nitric oxide generator, S-nitrosoglutathione (GSNO) reversibly inhibited oxygen utilisation with all substrates tested. The visible absorption spectra of the inhibited mitochondria showed that cytochromes c+c1, b and a+a3 were reduced, indicating a block at the distal end of the respiratory chain. Analysis of the respiratory chain enzyme activities in the presence of GSNO localised the site of inhibition of cytochrome c oxidase alone. These results indicate that nitric oxide is capable of rapidly and reversibly inhibiting the mitochondrial respiratory chain and may be implicated in the cytotoxic effects of nitric oxide in the CNS and other tissues.
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“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 [94]
In the citing paper
“Furthermore, S-nitrosation of mitochondrial targets can modify mitochondrial function (97, 98, 474).”
From Redox regulation of mitochondrial function (2012) · cites this paper as [97]
In the citing paper
“other studies have found a role for NO· in the inhibition of complex IV (cytochrome c oxidase) (97, 474) or in the ATPase complex (405).”
From Redox regulation of mitochondrial function (2012) · cites this paper as [97]
In the citing paper
“indicating that there was no ‘compensatory’ increased contribution of anaerobic glycolysis to energy turnover as may be the case if, for example, nitrate supplementation had resulted in an inhibition of respiration [62, 63].”
From Dietary Nitrate Supplementation and Exercise Performance (2014) · cites this paper as [63]
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Metadata
- Authors
- Cleeter, M. W. J., Cooper, J. M., Darley-Usmar, V. M., Moncada, S., & Schapira, A. H. V.
- Affiliations
- Royal Free London NHS Foundation Trust (GB)
- Wellcome Trust (GB)
- Venue
- FEBS Letters
- Publisher
- Wiley
- Published
- 1994-05-23
- Volume
- 345
- Issue
- 1
- Pages
- 50-54
- ISSN
- 0014-5793 (ISSN-L)
- 1873-3468
- OpenAlex
- W1528220495
- Cited by
- 1,241
- References
- 32
- Citations by year
- 2026: 21 · 2025: 14 · 2024: 24 · 2023: 14 · 2022: 15 · 2021: 26 · 2020: 27 · 2019: 27 · 2018: 28 · 2017: 32 · 2016: 31 · 2015: 37 · 2014: 41 · 2013: 33 · 2012: 49
- FWCI
- 12.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- FEBS Letters (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- nitric oxide, cytochrome c oxidase, reversible inhibition, mitochondrial respiratory chain, S-nitrosoglutathione, skeletal muscle mitochondria, oxygen utilisation, cytochrome reduction
- MeSH terms
- Animals, Electron Transport Complex IV, Electron Transport, Glutathione, Mitochondria, Muscle, Nitric Oxide, Nitroso Compounds, Parkinson Disease, S-Nitrosoglutathione, Rats
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