The DOI matches its Crossref record; 38 of the 38 references it cites were found in a registry or an index.
Persistent inhibition of cell respiration by nitric oxide: Crucial role of S -nitrosylation of mitochondrial complex I and protective action of glutathione
Open accessAbstract
Both reversible and irreversible inhibition of mitochondrial respiration have been reported following the generation of nitric oxide (NO) by cells. Using J774 cells, we have studied the effect of long-term exposure to NO on different enzymes of the respiratory chain. Our results show that, although NO inhibits complex IV in a way that is always reversible, prolonged exposure to NO results in a gradual and persistent inhibition of complex I that is concomitant with a reduction in the intracellular concentration of reduced glutathione. This inhibition appears to result from S -nitrosylation of critical thiols in the enzyme complex because it can be immediately reversed by exposing the cells to high intensity light or by replenishment of intracellular reduced glutathione. Furthermore, decreasing the concentration of reduced glutathione accelerates the process of persistent inhibition. Our results suggest that, although NO may regulate cell respiration physiologically by its action on complex IV, long-term exposure to NO leads to persistent inhibition of complex I and potentially to cell pathology.
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In the citing paper
“may result from the potential for excess nitric oxide to disrupt mitochondrial oxidative capacity (Bolanos et al. 1996; Clementi et al. 1998)”
From Oral nitrate and citrulline decrease blood pressure and increase vascular conductance in young adults: a potential therapy for heart failure (2016) · cites this paper as Clementi et al. 1998
In the citing paper
“previous work has shown that complex I is inhibited by various nitric oxide donors in vitro and that this inhibition is associated with S-nitrosation2,10,11,21–24.”
From Cardioprotection by S-nitrosation of a cysteine switch on mitochondrial complex I (2013) · cites this paper as [21]
In the citing paper
“Higher NO levels have been shown to persistently inhibit Complex I [210, 211] in macrophages, via oxidation or S-nitrosation of specific thiols.”
From Signaling and stress: The redox landscape in NOS2 biology (2015) · cites this paper as [211]
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 [98]
In the citing paper
“Earlier studies had previously provided evidence that exogenous NO· donors could inhibit complex I in whole cells by a mechanism that can be attenuated by low-molecular-weight thiol antioxidants, such as dithiothreitol or GSH, or by light of the appropriate action spectrum for –S-NO species, suggesting a role for –S-NO formation in this inhibitory effect (98).”
From Redox regulation of mitochondrial function (2012) · cites this paper as [98]
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Metadata
- Authors
- Clementi, E., Brown, G. C., Feelisch, M., & Moncada, S.
- Affiliations
- University of Cambridge (GB)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1998-06-23
- Volume
- 95
- Issue
- 13
- Pages
- 7631-7636
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC22706
- OpenAlex
- W2107366065
- Cited by
- 863
- References
- 38
- Citations by year
- 2026: 14 · 2025: 22 · 2024: 23 · 2023: 20 · 2022: 22 · 2021: 29 · 2020: 29 · 2019: 28 · 2018: 28 · 2017: 35 · 2016: 23 · 2015: 21 · 2014: 31 · 2013: 29 · 2012: 38
- FWCI
- 12.90
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- ePrints Soton (University of Southampton) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Wellcome Trust
- Topics
- 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
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Keywords
- nitric oxide, mitochondrial respiration, complex I, S-nitrosylation, glutathione, cytochrome c oxidase, electron transport inhibition, J774 macrophages, oxidative stress
- MeSH terms
- Animals, Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone, Cells, Cultured, Glutathione, Macrophages, Mitochondria, Nitric Oxide, Nitroso Compounds, Oxygen Consumption, Triazenes, Uncoupling Agents, NAD(P)H Dehydrogenase (Quinone), Mice
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