The 49-KDa Subunit of NADH-Ubiquinone Oxidoreductase (Complex I) Is Involved in the Binding of Piericidin and Rotenone, Two Quinone-Related Inhibitors
Abstract
Piericidin is a potent inhibitor of the mitochondrial and bacterial type I NADH‐ubiquinone oxidoreductases (Complex I) and is considered to bind at or close to the ubiquinone binding site(s) of the enzyme. Piericidin‐resistant mutants of the bacterium Rhodobacter capsulatus have been isolated and the present work demonstrates that a single missense mutation at the level of the gene encoding the peripheral 49‐kDa/NUOD subunit of Complex I is definitely associated with this resistance. Based on this original observation, we propose a model locating the binding site for piericidin (and quinone) at the interface between the hydrophilic and hydrophobic domains of Complex I.
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Piericidin A inhibits the mitochondrial NADH:ubiquinone oxidoreductase (complex I) by binding at or close to the ubiquinone binding site of the enzyme.
“Piericidin A inhibits the mitochondrial NADH:ubiquinone oxidoreductase (complex I) by binding at or close to the ubiquinone binding site of the enzyme [44].”
From Proliferating Astrocytes in Primary Culture Do Not Depend upon Mitochondrial Respiratory Complex I Activity or Oxidative Phosphorylation (2023) · cites this paper as [44]
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- Authors
- Darrouzet, E., Issartel, J.-P., Lunardi, J., & Dupuis, A.
- Affiliations
- Université Joseph Fourier (FR)
- Corresponding author
- Dupuis, Alain
- Venue
- FEBS Letters
- Publisher
- Wiley
- Published
- 1998-07-10
- Volume
- 431
- Issue
- 1
- Pages
- 34-38
- ISSN
- 0014-5793 (ISSN-L)
- 1873-3468
- OpenAlex
- W2067434074
- Cited by
- 122
- References
- 0
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 1 · 2022: 4 · 2021: 4 · 2020: 4 · 2019: 5 · 2018: 4 · 2017: 2 · 2016: 2 · 2015: 4 · 2014: 8 · 2013: 1 · 2012: 4
- FWCI
- 3.02
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- FEBS Letters (publishedVersion)
- PubMed (publishedVersion)
- 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
- complex I, piericidins, rotenone, ubiquinone binding site, Rhodobacter capsulatus, missense mutations, inhibitor resistance, mitochondrial respiratory chain
- MeSH terms
- Amino Acid Sequence, Anti-Bacterial Agents, Binding Sites, Drug Resistance, Microbial, Enzyme Inhibitors, Molecular Sequence Data, Mutation, Pyridines, Quinones, Rotenone, Rhodobacter capsulatus, NAD(P)H Dehydrogenase (Quinone)
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