title: Idebenone-induced recovery of glycerol-3-phosphate and succinate oxidation inhibited by digitonin.
abstract: Digitonin solubilizes mitochondrial membrane, breaks the integrity of the respiratory chain and releases two mobile redox-active components: coenzyme Q (CoQ) and cytochrome c (cyt c). In the present study we report the inhibition of glycerol-3-phosphate- and succinate-dependent oxygen consumption rates by digitonin treatment. Our results show that the inhibition of oxygen consumption rates is recovered by the addition of exogenous synthetic analog of CoQ idebenone (hydroxydecyl-ubiquinone; IDB) and cyt c. Glycerol-3-phosphate oxidation rate is recovered to 148 % of control values, whereas succinate-dependent oxidation rate only to 68 %. We find a similar effect on the activities of glycerol-3-phosphate and succinate cytochrome c oxidoreductase. Our results also indicate that succinate-dependent oxidation is less sensitive to digitonin treatment and less activated by IDB in comparison with glycerol-3-phosphate-dependent oxidation. These findings might indicate the different mechanism of the electron transfer from two flavoprotein-dependent dehydrogenases (glycerol-3-phosphate dehydrogenase and succinate dehydrogenase) localized on the outer and inner face of the inner mitochondrial membrane, respectively.
authors.affiliation: Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic. rauchova@biomed.cas.cz
authors.forename: H
authors.initials: H
authors.lastname: Rauchová
authors.forename: M
authors.initials: M
authors.lastname: Vokurková
authors.forename: Z
authors.initials: Z
authors.lastname: Drahota
mesh_terms: D000818:Animals; D045304:Cytochromes c / Q000378:metabolism; D004072:Digitonin / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005993:Glycerolphosphate Dehydrogenase / Q000378:metabolism; D005994:Glycerophosphates / Q000378:metabolism*; D006980:Hyperthyroidism / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000378:metabolism; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function; D013384:Succinate Cytochrome c Oxidoreductase / Q000378:metabolism; D019802:Succinic Acid / Q000378:metabolism*; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D005994:Glycerophosphates; D014451:Ubiquinone; D045304:Cytochromes c; D019802:Succinic Acid; D013384:Succinate Cytochrome c Oxidoreductase; D005993:Glycerolphosphate Dehydrogenase; C036619:idebenone; D004072:Digitonin