title: A mitochondria-targeted antioxidant can inhibit peroxidase activity of cytochrome c by detachment of the protein from liposomes.
abstract: Interaction of cytochrome c with cardiolipin converts this respiratory chain electron-transfer protein into a peroxidase, supposedly involved in mitochondria-mediated apoptosis initiation. Liposome membrane permeabilization provoked by peroxidase activity of the cytochrome c/cardiolipin complex has been previously shown to be suppressed by conventional antioxidants. Here, the mitochondria-targeted antioxidant SkQ1 (plastoquinonyl-decyl-triphenylphosphonium) was found to strongly inhibit both cytochrome c/cardiolipin peroxidase activity and the permeabilization of liposomes composed of phosphatidylcholine and cardiolipin. A number of binding assays revealed a significant inhibiting effect of SkQ1 on cytochrome c binding to liposomes, thus suggesting that SkQ1-mediated protection of liposomes from the cytochrome c/H2 O2 -induced permeabilization involved distortion of the cytochrome c-membrane binding. It is suggested that antioxidant and antiapoptotic effects of alkyltriphenylphosphonium cations can be related to the prevention of cytochrome c/cardiolipin interaction.
authors.affiliation: Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Russia.|Department of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Russia.
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Firsov
authors.affiliation: Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Russia.
authors.forename: Elena A
authors.initials: EA
authors.lastname: Kotova
authors.affiliation: Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Russia.
authors.forename: Viktor N
authors.initials: VN
authors.lastname: Orlov
authors.affiliation: Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Russia.
authors.forename: Yuri N
authors.initials: YN
authors.lastname: Antonenko
authors.affiliation: Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Russia.|Department of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Russia.
authors.forename: Vladimir P
authors.initials: VP
authors.lastname: Skulachev
mesh_terms: D000975:Antioxidants / Q000378:metabolism* / Q000494:pharmacology; D002308:Cardiolipins / Q000096:biosynthesis*; D045304:Cytochromes c / Q000096:biosynthesis*; D004579:Electron Transport / Q000187:drug effects; D008081:Liposomes / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction; D009195:Peroxidase / Q000096:biosynthesis*; D010971:Plastoquinone / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: C532038:10-(6'-plastoquinonyl)decyltriphenylphosphonium; D000975:Antioxidants; D002308:Cardiolipins; D008081:Liposomes; D045304:Cytochromes c; D009195:Peroxidase; D010971:Plastoquinone
keywords: antioxidant; binding; cardiolipin; cytochrome c; leakage; liposome