Identification of the Mitochondrial ND3 Subunit as a Structural Component Involved in the Active/Deactive Enzyme Transition of Respiratory Complex I
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Mitochondrial complex I (NADH:ubiquinone oxidoreductase) undergoes reversible deactivation upon incubation at 30-37 degrees C. The active/deactive transition could play an important role in the regulation of complex I activity. It has been suggested recently that complex I may become modified by S-nitrosation under pathological conditions during hypoxia or when the nitric oxide:oxygen ratio increases. Apparently, a specific cysteine becomes accessible to chemical modification only in the deactive form of the enzyme. By selective fluorescence labeling and proteomic analysis, we have identified this residue as cysteine-39 of the mitochondrially encoded ND3 subunit of bovine heart mitochondria. Cysteine-39 is located in a loop connecting the first and second transmembrane helix of this highly hydrophobic subunit. We propose that this loop connects the ND3 subunit of the membrane arm with the PSST subunit of the peripheral arm of complex I, placing it in a region that is known to be critical for the catalytic mechanism of complex I. In fact, mutations in three positions of the loop were previously reported to cause Leigh syndrome with and without dystonia or progressive mitochondrial disease.
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Cys39 of ND3 has been shown to become exposed under hypoxia or lack of NADH that result in low complex I activity due to the active-deactive transition.
“Notably, one of these, Cys39 of the ND3 subunit, has been shown to become exposed under conditions of hypoxia or lack of NADH that result in low complex I activity due to the active-deactive transition26–28.”
From Cardioprotection by S-nitrosation of a cysteine switch on mitochondrial complex I (2013) · cites this paper as [26]
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Self-citation
- Authors
- Galkin, A., Meyer, B., Wittig, I., Karas, M., Schägger, H., Vinogradov, A., & Brandt, U.
- Affiliations
- Goethe University Frankfurt (DE)
- Lomonosov Moscow State University (RU)
- Corresponding author
- Brandt, Ulrich
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2008-07
- Volume
- 283
- Issue
- 30
- Pages
- 20907-20913
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC2475694
- OpenAlex
- W2030408645
- Cited by
- 147
- References
- 42
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 6 · 2023: 3 · 2022: 10 · 2021: 6 · 2020: 15 · 2019: 12 · 2018: 13 · 2017: 11 · 2016: 11 · 2015: 10 · 2014: 12 · 2013: 12 · 2012: 4
- FWCI
- 1.92
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Publication Server of Goethe University Frankfurt am Main (Goethe University Frankfurt) (submittedVersion, cc-by)
- Research Portal (Queen's University Belfast) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft ((EXC 115).)
- National Institutes of Health
- Fogarty International Center (#R03 TW07825, R03TW007825)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Coenzyme Q10 studies and effects
- Keywords
- mitochondrial complex I, enzyme inactivation, S-nitrosylation, Leigh syndrome, mitochondrial disease, bovine heart mitochondria
- MeSH terms
- Animals, Catalysis, Cattle, Chymotrypsin, Cysteine, Electrophoresis, Polyacrylamide Gel, Fluorescent Dyes, Models, Biological, Myocardium, Nitric Oxide, Oxygen, Mass Spectrometry, Mitochondrial Diseases, Proteomics, Electron Transport Complex I
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