Ferulenol specifically inhibits succinate ubiquinone reductase at the level of the ubiquinone cycle.
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.
Lahouel
Mesbah
M
Département de pharmacologie et phytochimie, Université de Jijel, Algeria.
Zini
Roland
R
Zellagui
Ammar
A
Rhouati
Salah
S
Carrupt
Pierre-Alain
PA
Morin
Didier
D
D000818:Animals; D003374:Coumarins / Q000302:isolation & purification / Q000494:pharmacology*; D042963:Electron Transport Complex II / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007700:Kinetics; D008930:Mitochondria, Liver / Q000201:enzymology*; D010101:Oxygen Consumption / Q000187:drug effects; D018517:Plant Roots; D006180:Proton-Translocating ATPases / Q000378:metabolism; D051381:Rats; D014451:Ubiquinone / Q000378:metabolism*
D003374:Coumarins; D004791:Enzyme Inhibitors; D014451:Ubiquinone; C092340:ferulenol; D042963:Electron Transport Complex II; D006180:Proton-Translocating ATPases