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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
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]
Citations
Cites
Beckman, J. S., Beckman, T. W., Chen, J., Marshall, P. A., & Freeman, B. A. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.4.1620 · Cited by 7,029
Vascular endothelial cells synthesize nitric oxide from L-arginine
Palmer, R. M. J., Ashton, D., & Moncada, S. (1988) · Nature · doi:10.1038/333664a0 · Cited by 4,786
Self-citationStuehr, D. J., & Nathan, C. F. (1989) · The Journal of Experimental Medicine · doi:10.1084/jem.169.5.1543 · Cited by 1,744
Griffith, O. W., & Meister, A. (1979) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)35980-5 · Cited by 1,683
The chemistry of peroxynitrite: A product from the reaction of nitric oxide with superoxide
Pryor, W. A., & Squadrito, G. L. (1995) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.1995.268.5.l699 · Cited by 1,511
Mitochondrial control of apoptosis
Kroemer, G., Zamzami, N., & Susín, S. A. (1997) · Immunology Today · doi:10.1016/s0167-5699(97)80014-x · Cited by 1,476
Cleeter, M. W. J., Cooper, J. M., Darley-Usmar, V. M., Moncada, S., & Schapira, A. H. V. (1994) · FEBS Letters · doi:10.1016/0014-5793(94)00424-2 · Cited by 1,241
Self-citationUbisemiquinone is the electron donor for superoxide formation by complex III of heart mitochondria
Turrens, J. F., Alexandre, A., & Lehninger, A. L. (1985) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(85)90293-0 · Cited by 1,214
Brown, G. C., & Cooper, C. E. (1994) · FEBS Letters · doi:10.1016/0014-5793(94)01290-3 · Cited by 1,055
Self-citationActivation of the Cardiac Calcium Release Channel (Ryanodine Receptor) by Poly-S-Nitrosylation
Xu, L., Eu, J. P., Meissner, G., & Stamler, J. S. (1998) · Science · doi:10.1126/science.279.5348.234 · Cited by 991
Microglial-produced nitric oxide and reactive nitrogen oxides mediate neuronal cell death
Boje, K. M., & Arora, P. K. (1992) · Brain Research · doi:10.1016/0006-8993(92)91004-x · Cited by 944
Cadenas, E., Boveris, A., Ragan, C. I., & Stoppani, A. O. M. (1977) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(77)90035-2 · Cited by 855
Dimmeler, S., Haendeler, J., Nehls, M. C., & Zeiher, A. M. (1997) · The Journal of Experimental Medicine · doi:10.1084/jem.185.4.601 · Cited by 806
Microglial cell cytotoxicity of oligodendrocytes is mediated through nitric oxide.
Merrill, J. E., Ignarro, L. J., Sherman, M. P., Melinek, J., & Lane, T. E. (1993) · The Journal of Immunology · doi:10.4049/jimmunol.151.4.2132 · Cited by 782
The NADH:ubiquinone oxidoreductase (complex I) of respiratory chains
Walker, J. E. (1992) · Quarterly Reviews of Biophysics · doi:10.1017/s003358350000425x · Cited by 777
Methods in Nitric Oxide Research
Young, J. (1997) · Physiological Measurement · doi:10.1088/0967-3334/18/1/008 · Cited by 749
Inhibition of Mitochondrial Electron Transport by Peroxynitrite
Radi, R., Rodriguez, M., Castro, L., & Telleri, R. (1994) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1994.1013 · Cited by 693
New nitric oxide-releasing zwitterions derived from polyamines
Hrabie, J. A., Klose, J. R., Wink, D. A., & Keefer, L. K. (1993) · The Journal of Organic Chemistry · doi:10.1021/jo00058a030 · Cited by 593
Drapier, J., & Hibbs, J. B. (1988) · The Journal of Immunology · doi:10.4049/jimmunol.140.8.2829 · Cited by 592
Aconitase is readily inactivated by peroxynitrite, but not by its precursor, nitric oxide.
Castro, L., Rodriguez, M., & Radi, R. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)43894-x · Cited by 589
Superoxide and peroxynitrite inactivate aconitases, but nitric oxide does not.
Hausladen, A., & Fridovich, I. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)43893-8 · Cited by 585
Diamide, a new reagent for the intracellular oxidation of glutathione to the disulfide
Kosower, N. S., Kosower, E. M., Wertheim, B., & Correa, W. S. (1969) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(69)90850-x · Cited by 525
Bolaños, J. P., Almeida, Á., Stewart, V. C., Peuchen, S., Land, J. M., Clark, J. B., & Heales, S. (1997) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1997.68062227.x · Cited by 519
Bolaños, J. P., Heales, S., Land, J. M., & Clark, J. B. (1995) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1995.64051965.x · Cited by 492
S-nitrosylation regulates apoptosis
Melino, G., Bernassola, F., Knight, R. A., Corasaniti, M. T., Nistic, G., & Finazzi‐Agrò, A. (1997) · Nature · doi:10.1038/41237 · Cited by 446
Nitric Oxide‐Mediated Inhibition of the Mitochondrial Respiratory Chain in Cultured Astrocytes
Bolaños, J. P., Peuchen, S., Heales, S., Land, J. M., & Clark, J. B. (1994) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1994.63030910.x · Cited by 413
Effect of exogenous and endogenous nitric oxide on mitochondrial respiration of rat hepatocytes
Stadler, J., Billiar, T. R., CURRAN, R. D., Stuehr, D. J., Ochoa, J. B., & Simmons, R. L. (1991) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1991.260.5.c910 · Cited by 396
Sites of inhibition of mitochondrial electron transport in macrophage-injured neoplastic cells.
Granger, D. L., & Lehninger, A. L. (1982) · The Journal of Cell Biology · doi:10.1083/jcb.95.2.527 · Cited by 346
Lizasoaín, I., Moro, M. Á., Knowles, R. G., Darley-Usmar, V. M., & Moncada, S. (1996) · Biochemical Journal · doi:10.1042/bj3140877 · Cited by 318
Self-citationInactivation of succinate dehydrogenase by 3-nitropropionate.
Coles, C. J., Edmondson, D. E., & Singer, T. P. (1979) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)50574-3 · Cited by 307
Mitochondria: A practical approach
Jacobs, H. T. (1988) · Trends in Genetics · doi:10.1016/0168-9525(88)90164-3 · Cited by 292
Geng, Y., Hansson, G. K., & Holme, E. (1992) · Circulation Research · doi:10.1161/01.res.71.5.1268 · Cited by 272
Nitric oxide-mediated mitochondrial damage: A potential neuroprotective role for glutathione
Bolaños, J. P., Heales, S. J. R., Peuchen, S., Barker, J. E., Land, J. M., & Clark, J. B. (1996) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(96)00240-7 · Cited by 263
Mohr, S., Stamler, J. S., & Brüne, B. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.8.4209 · Cited by 251
Turning on the respiratory burst
Baggiolini, M., & Wymann, M. P. (1990) · Trends in Biochemical Sciences · doi:10.1016/0968-0004(90)90179-f · Cited by 210
Nitric oxide produced by activated astrocytes rapidly and reversibly inhibits cellular respiration
Brown, G. C., Bolaños, J. P., Heales, S., & Clark, J. B. (1995) · Neuroscience Letters · doi:10.1016/0304-3940(95)11703-y · Cited by 205
Self-citationCytochromecoxidase: some current biochemical and biophysical problems
Malmström, B. G. (1973) · Quarterly Reviews of Biophysics · doi:10.1017/s0033583500001578 · Cited by 159
Kiyotaki, C., Peisach, J., & Bloom, B. R. (1984) · The Journal of Immunology · doi:10.4049/jimmunol.132.2.857 · Cited by 58
Flagged first, then by citations
Research works printed but not linked: 2
- W A Pryor, G L Squadrito Am J Physiol 268, L699–L722 (1995).
- L Xu, J P Eu, G Meissner, J S Stamler Nature (London) 279, 234–237 (1998).
Cited by
Sorted by citations
A guide to immunometabolism for immunologists
O'Neill, L. A. J., Kishton, R. J., & Rathmell, J. (2016) · Nature Reviews Immunology · doi:10.1038/nri.2016.70 · Cited by 3,315
The nitrate-nitrite-nitric oxide pathway in physiology and therapeutics
Lundberg, J. O., Weitzberg, E., & Gladwin, M. T. (2008) · Nature Reviews Drug Discovery · doi:10.1038/nrd2466 · Cited by 2,739
Oxidative stress in Parkinson's disease
Jenner, P. (2003) · Annals of Neurology · doi:10.1002/ana.10483 · Cited by 2,053
Metabolic reprogramming in macrophages and dendritic cells in innate immunity
Kelly, B., & O'Neill, L. A. (2015) · Cell Research · doi:10.1038/cr.2015.68 · Cited by 1,876
Metabolic Pathways in Immune Cell Activation and Quiescence
Pearce, E. L., & Pearce, E. J. (2013) · Immunity · doi:10.1016/j.immuni.2013.04.005 · Cited by 1,692
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
