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Title: 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:
 [1];  [2];  [3];  [4];  [4];  [5];  [2];  [3];
  1. Departement de pharmacologie et phytochimie, Universite de Jijel (Algeria)
  2. INSERM U841, Creteil F-94010 (France)
  3. (France)
  4. Laboratoire des substances naturelles, Universite de Constantine (Algeria)
  5. 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}
}