title: Ubiquinol and plastoquinol triphenylphosphonium conjugates can carry electrons through phospholipid membranes.
abstract: Many mitochondria-targeted antioxidants (MTAs) that comprise a quinol moiety covalently attached through an aliphatic carbon chain to the lipophilic triphenylphosphonium cation are widely used for evaluating the role of mitochondria in pathological processes involving oxidative stress. The potency of MTAs to carry electrons across biological membranes and thereby mediate transmembrane redox processes was unknown. To assess this, we measured the rate of ferricyanide reduction inside liposomes by external ascorbate. Here, we show that MTAs containing ubiquinone (MitoQ series) or plastoquinone (SkQ series) can carry electrons through lipid membranes, with the rate being inversely proportional to the length of the hydrocarbon linker group. Furthermore, this process was stimulated by the hydrophobic anion tetraphenylborate suggesting that permeation of the cationic MTA through the membrane was the rate-limiting step of the process. This conclusion was supported by the observation that the rate of MTA-induced electron transfer was insensitive to nigericin, in contrast to electron transfer mediated by neutral quinone derivatives. These findings indicate that MTAs can be utilized to transfer electrons across lipid membranes and this may be applicable to the study of the electron-transport chain in mitochondria and other natural membranes exhibiting redox processes.
authors.affiliation: Lomonosov Moscow State University, Belozersky Institute of Physico-Chemical Biology, Vorobyevy Gory 1, Moscow 119991, Russia; Lomonosov Moscow State University, Institute of Mitoengineering, Vorobyevy Gory 1, Moscow 119991, Russia. Electronic address: antonen@genebee.msu.ru.
authors.forename: Tatyana I
authors.initials: TI
authors.lastname: Rokitskaya
authors.affiliation: Medical Research Council Mitochondrial Biology Unit, Wellcome Trust/MRC Building, Hills Road, Cambridge CB2 0XY, UK.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Murphy
authors.affiliation: Lomonosov Moscow State University, Belozersky Institute of Physico-Chemical Biology, Vorobyevy Gory 1, Moscow 119991, Russia; Lomonosov Moscow State University, Institute of Mitoengineering, Vorobyevy Gory 1, Moscow 119991, Russia; Lomonosov Moscow State University, Faculty of Bioengineering and Bioinformatics, Vorobyevy Gory 1, Moscow 119991, Russia.
authors.forename: Vladimir P
authors.initials: VP
authors.lastname: Skulachev
authors.affiliation: Lomonosov Moscow State University, Belozersky Institute of Physico-Chemical Biology, Vorobyevy Gory 1, Moscow 119991, Russia; Lomonosov Moscow State University, Institute of Mitoengineering, Vorobyevy Gory 1, Moscow 119991, Russia. Electronic address: rokitskaya@genebee.msu.ru.
authors.forename: Yuri N
authors.initials: YN
authors.lastname: Antonenko
mesh_terms: D002462:Cell Membrane / Q000737:chemistry* / Q000378:metabolism; D004579:Electron Transport; D005292:Ferricyanides / Q000737:chemistry / Q000378:metabolism; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D010743:Phospholipids / Q000737:chemistry* / Q000378:metabolism; D010971:Plastoquinone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism
chemical_list: D005292:Ferricyanides; D008051:Lipid Bilayers; D010743:Phospholipids; D014451:Ubiquinone; C007931:hexacyanoferrate III; C003165:plastoquinol; C003741:ubiquinol; D010971:Plastoquinone
keywords: Bilayer lipid membrane; Liposome; Mitochondria-targeted antioxidant; Redox mediator