Direct evidence for S-nitrosation of mitochondrial complex I
Open accessAbstract
NO• (nitric oxide) is a pleiotropic signalling molecule, with many of its effects on cell function being elicited at the level of the mitochondrion. In addition to the well-characterized binding of NO• to the CuB/haem-a3 site in mitochondrial complex IV, it has been proposed by several laboratories that complex I can be inhibited by S-nitrosation of a cysteine. However, direct molecular evidence for this is lacking. In this investigation we have combined separation techniques for complex I (blue-native gel electrophoresis, Superose 6 column chromatography) with sensitive detection methods for S-nitrosothiols (chemiluminescence, biotin-switch assay), to show that the 75 kDa subunit of complex I is S-nitrosated in mitochondria treated with S-nitrosoglutathione (10 μM–1 mM). The stoichiometry of S-nitrosation was 7:1 (i.e. 7 mol of S-nitrosothiols per mol of complex I) and this resulted in significant inhibition of the complex. Furthermore, S-nitrosothiols were detected in mitochondria isolated from hearts subjected to ischaemic preconditioning. The implications of these results for the physiological regulation of respiration, for reactive oxygen species generation and for a potential role of S-nitrosation in cardioprotection are discussed.
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Prior work showed that complex I is inhibited by various nitric oxide donors in vitro and that this inhibition is associated with S-nitrosation.
“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 [22]
Endogenously produced NO· causes S-nitrosation of complex I during ischemic preconditioning in Langendorff perfused hearts.
“Using Langendorff perfused hearts, endogenously produced NO· was found to cause S-nitrosation of complex I during ischemic preconditioning (57)”
From Redox regulation of mitochondrial function (2012) · cites this paper as [57]
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References 51 · Cited by 274
Research works printed but not linked: 5
- Stamler, J. S., Lamas, S. and Fang, F. C. (2001) Nitrosylation: the prototypic redox-based signalling mechanism. Cell (Cambridge, Mass.) 106, 675-683
- Stamler, J. S., Jaraki, O., Osborne, J., Simon, D. I., Keaney, J., Vita, J., Singel, D., Valeri, C. R. and Loscalzo, J. (1992) Nitric oxide circulates in mammalian plasma primarily as an S-nitroso adduct of serum albumin. Proc. Natl. Acad. Sci. U.S.A. 89, 7674-7677
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- Moro, M. A., Darley-Usmar, V. M., Goodwin, D. A., Read, N. G., Zamora-Pino, R., Feelisch, M., Radomski, M. W. and Moncada, S. (1994) Paradoxical fate and biological action of peroxynitrite on human platelets. Proc. Natl. Acad. Sci. U.S.A. 91, 6702-6706
- Zweier, J. L., Flaherty, J. T. and Weisfeldt, M. L. (1987) Direct measurement of free radical generation following reperfusion of ischaemic myocardium. Proc. Natl. Acad. Sci. U.S.A. 84, 1404-1407 47
- Authors
- Burwell, L. S., Nadtochiy, S. M., Tompkins, A. J., Young, S., & Brookes, P. S.
- Affiliations
- University of Rochester Medicine (US)
- Venue
- Biochemical Journal
- Publisher
- Portland Press Ltd.
- Published
- 2006-02-24
- Volume
- 394
- Issue
- 3
- Pages
- 627-634
- ISSN
- 0264-6021 (ISSN-L)
- 1470-8728
- OpenAlex
- W2020937749
- Cited by
- 274
- References
- 51
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 8 · 2023: 2 · 2022: 3 · 2021: 2 · 2020: 6 · 2019: 8 · 2018: 12 · 2017: 20 · 2016: 11 · 2015: 12 · 2014: 23 · 2013: 17 · 2012: 23
- FWCI
- 10.62
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Biochemical Journal (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Rochester
- National Institutes of Health
- National Heart, Lung, and Blood Institute (HL71158, R01HL071158)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- S-nitrosylation, mitochondrial complex I, nitric oxide, S-nitrosothiols, S-nitrosoglutathione, mitochondrial complex I inhibition, ischemic preconditioning, heart mitochondria, cardioprotection, reactive oxygen species
- MeSH terms
- Animals, Male, Mitochondria, Myocardium, Nitrates, Sensitivity and Specificity, Nitrosation, Rats, Sprague-Dawley, Ischemic Preconditioning, Myocardial, S-Nitrosothiols, Electron Transport Complex I, Rats
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