Cited by 122Mitochondrial Function and PathologyNitric Oxide and Endothelin EffectsRedox biology and oxidative stress

S-Nitrosation of Mitochondrial Complex I Depends on Its Structural Conformation

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Galkin, Alexander, Moncada, Salvador·2007·Journal of Biological Chemistry

Abstract

Nitric oxide is known to cause persistent inhibition of mitochondrial respiration as a result of S-nitrosation of NADH: ubiquinone oxidoreductase (complex I) (Clementi, E., Brown, G. C., Feelisch, M., and Moncada, S. (1998) Proc. Natl. Acad. Sci. U. S. A. 95, 7631-7636). Little is known about whether such nitrosation occurs in physiological conditions and, if so, what are the possible cellular mechanisms. We have now found that the conformational state (active/deactive transition (Vinogradov, A. D. (1998) Biochim. Biophys. Acta 1364, 169-185)) of mitochondrial complex I is an important factor for the interaction of the enzyme with nitrosothiols and peroxynitrite. Only the deactivated, idle form of complex I was susceptible to inhibition by nitrosothiols and peroxynitrite. In contrast, the active form of the enzyme was insensitive to such treatment. Neither form of complex I was inhibited by nitric oxide itself. Our data suggest that the process of active/deactive transition plays an important role in the regulation of complex I activity and cellular respiration by nitric oxide. The implications of this finding for hypoxic or pathophysiological conditions in vivo 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.”

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  1. Clementi, E., Brown, G. C., Feelisch, M., and Moncada, S. (1998) Proc. Natl. Acad. Sci. U. S. A. 95, 7631-7636
  2. Palacios-Callender, M., Quintero, M., Hollis, V. S., Springett, R. J., and Moncada, S. (2004) Proc. Natl. Acad. Sci. U. S. A. 101, 7630 -7635

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Authors
Galkin, A., & Moncada, S.
Affiliations
University College London (GB)
Corresponding author
Galkin, Alexander
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2007-12
Volume
282
Issue
52
Pages
37448-37453
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2086448760
Cited by
122
References
46
Citations by year
2026: 1 · 2025: 2 · 2024: 1 · 2023: 4 · 2022: 6 · 2021: 6 · 2020: 5 · 2019: 6 · 2018: 7 · 2017: 9 · 2016: 8 · 2015: 8 · 2014: 12 · 2013: 10 · 2012: 6
FWCI
3.05
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research Explorer (The University of Manchester) (publishedVersion)
  • UCL Discovery (University College London) (submittedVersion)
  • Research Portal (Queen's University Belfast) (submittedVersion)
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, peroxynitrite, complex I, mitochondrial respiration inhibition, hypoxia
MeSH terms
Animals, Hypoxia, Cattle, Mitochondria, Heart, Models, Biological, Molecular Conformation, Multienzyme Complexes, Myocardium, NAD, NADH, NADPH Oxidoreductases, Nitric Oxide, Sulfhydryl Compounds, Superoxides, Time Factors, Oxidative Stress, Peroxynitrous Acid, Electron Transport Complex I

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