Ferulenol specifically inhibits succinate ubiquinone reductase at the level of the ubiquinone cycle
Abstract
The natural compound ferulenol, a sesquiterpene prenylated coumarin derivative, was purified from Ferula vesceritensis and its mitochondrial effects were studied. Ferulenol caused inhibition of oxidative phoshorylation. At low concentrations, ferulenol inhibited ATP synthesis by inhibition of the adenine nucleotide translocase without limitation of mitochondrial respiration. At higher concentrations, ferulenol inhibited oxygen consumption. Ferulenol caused specific inhibition of succinate ubiquinone reductase without altering succinate dehydrogenase activity of the complex II. This inhibition results from a limitation of electron transfers initiated by the reduction of ubiquinone to ubiquinol in the ubiquinone cycle. This original mechanism of action makes ferulenol a useful tool to study the physiological role and the mechanism of electron transfer in the complex II. In addition, these data provide an additional mechanism by which ferulenol may alter cell function and demonstrate that mitochondrial dysfunction is an important determinant in Ferula plant toxicity.
- Authors:
- Departement de pharmacologie et phytochimie, Universite de Jijel (Algeria)
- INSERM U841, Creteil F-94010 (France)
- (France)
- Laboratoire des substances naturelles, Universite de Constantine (Algeria)
- LCT-Pharmacochimie, Section des Sciences Pharmaceutiques, Universite de Geneve (Switzerland)
- Publication Date:
- OSTI Identifier:
- 20979861
- Resource Type:
- Journal Article
- Resource Relation:
- Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 355; Journal Issue: 1; Other Information: DOI: 10.1016/j.bbrc.2007.01.145; PII: S0006-291X(07)00212-4; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 60 APPLIED LIFE SCIENCES; ADENINES; ATP; BIOSYNTHESIS; COMPLEXES; COUMARIN; ELECTRON TRANSFER; INHIBITION; MITOCHONDRIA; OXIDATION; OXYGEN; PHOSPHORYLATION; RESPIRATION; TOXICITY; UBIQUINONE
Citation Formats
Lahouel, Mesbah, Zini, Roland, Universite Paris 12, Faculte de Medecine, Laboratoire de Pharmacologie, Creteil F-94010, Zellagui, Ammar, Rhouati, Salah, Carrupt, Pierre-Alain, Morin, Didier, Universite Paris 12, Faculte de Medecine, Laboratoire de Pharmacologie, Creteil F-94010, and E-mail: didier.morin@creteil.inserm.fr. Ferulenol specifically inhibits succinate ubiquinone reductase at the level of the ubiquinone cycle. United States: N. p., 2007.
Web. doi:10.1016/j.bbrc.2007.01.145.
Lahouel, Mesbah, Zini, Roland, Universite Paris 12, Faculte de Medecine, Laboratoire de Pharmacologie, Creteil F-94010, Zellagui, Ammar, Rhouati, Salah, Carrupt, Pierre-Alain, Morin, Didier, Universite Paris 12, Faculte de Medecine, Laboratoire de Pharmacologie, Creteil F-94010, & E-mail: didier.morin@creteil.inserm.fr. Ferulenol specifically inhibits succinate ubiquinone reductase at the level of the ubiquinone cycle. United States. doi:10.1016/j.bbrc.2007.01.145.
Lahouel, Mesbah, Zini, Roland, Universite Paris 12, Faculte de Medecine, Laboratoire de Pharmacologie, Creteil F-94010, Zellagui, Ammar, Rhouati, Salah, Carrupt, Pierre-Alain, Morin, Didier, Universite Paris 12, Faculte de Medecine, Laboratoire de Pharmacologie, Creteil F-94010, and E-mail: didier.morin@creteil.inserm.fr. Fri .
"Ferulenol specifically inhibits succinate ubiquinone reductase at the level of the ubiquinone cycle". United States.
doi:10.1016/j.bbrc.2007.01.145.
@article{osti_20979861,
title = {Ferulenol specifically inhibits succinate ubiquinone reductase at the level of the ubiquinone cycle},
author = {Lahouel, Mesbah and Zini, Roland and Universite Paris 12, Faculte de Medecine, Laboratoire de Pharmacologie, Creteil F-94010 and Zellagui, Ammar and Rhouati, Salah and Carrupt, Pierre-Alain and Morin, Didier and Universite Paris 12, Faculte de Medecine, Laboratoire de Pharmacologie, Creteil F-94010 and E-mail: didier.morin@creteil.inserm.fr},
abstractNote = {The natural compound ferulenol, a sesquiterpene prenylated coumarin derivative, was purified from Ferula vesceritensis and its mitochondrial effects were studied. Ferulenol caused inhibition of oxidative phoshorylation. At low concentrations, ferulenol inhibited ATP synthesis by inhibition of the adenine nucleotide translocase without limitation of mitochondrial respiration. At higher concentrations, ferulenol inhibited oxygen consumption. Ferulenol caused specific inhibition of succinate ubiquinone reductase without altering succinate dehydrogenase activity of the complex II. This inhibition results from a limitation of electron transfers initiated by the reduction of ubiquinone to ubiquinol in the ubiquinone cycle. This original mechanism of action makes ferulenol a useful tool to study the physiological role and the mechanism of electron transfer in the complex II. In addition, these data provide an additional mechanism by which ferulenol may alter cell function and demonstrate that mitochondrial dysfunction is an important determinant in Ferula plant toxicity.},
doi = {10.1016/j.bbrc.2007.01.145},
journal = {Biochemical and Biophysical Research Communications},
number = 1,
volume = 355,
place = {United States},
year = {Fri Mar 30 00:00:00 EDT 2007},
month = {Fri Mar 30 00:00:00 EDT 2007}
}
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Inhibition of NADH-ubiquinone reductase activity by N,N'-dicyclohexylcarbodiimide and correlation of this inhibition with the occurrence of energy-coupling site 1 in various organisms
The NADH-ubiquinone reductase activity of the respiratory chains of several organisms was inhibited by the carboxyl-modifying reagent N,N'-dicyclohexylcarbodiimide (DCCD). This inhibition correlated with the presence of an energy-transducing site in this segment of the respiratory chain. Where the NADH-quinone reductase segment involved an energy-coupling site (e.g., in bovine heart and rat liver mitochondria, and in Paracoccus denitrificans, Escherichia coli, and Thermus thermophilus HB-8 membranes), DCCD acted as an inhibitor of ubiquinone reduction by NADH. By contrast, where energy-coupling site 1 was absent (e.g., in Saccharomyces cerevisiae mitochondria and BacilLus subtilis membranes), there was no inhibition of NADH-ubiquinone reductase activity bymore » -
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