Prevention of cardiolipin oxidation and fatty acid cycling as two antioxidant mechanisms of cationic derivatives of plastoquinone (SkQs)

被引：100

作者：

Skulachev, Vladimir P. ^{[1
,2
]}

Antonenko, Yury N. ^{[1
]}

Cherepanov, Dmitry A. ^{[3
]}

Chernyak, Boris V. ^{[1
]}

Izyumov, Denis S. ^{[1
]}

Khailova, Ludmila S.

Klishin, Sergey S. ^{[1
]}

Korshunova, Galina A. ^{[1
]}

Lyamzaev, Konstantin G. ^{[1
]}

Pletjushkina, Olga Yu. ^{[1
]}

Roginsky, Vitaly A. ^{[4
]}

Rokitskaya, Tatiana I. ^{[1
]}

Severin, Fedor F. ^{[1
]}

Severina, Inna I. ^{[1
,5
]}

Simonyan, Ruben A. ^{[1
]}

Skulachev, Maxim V. ^{[1
,6
]}

Sumbatyan, Natalia V. ^{[7
]}

Sukhanova, Evgeniya I. ^{[8
]}

Tashlitsky, Vadim N. ^{[7
]}

Trendeleva, Tatyana A. ^{[8
]}

Vyssokikh, Mikhail Yu. ^{[1
]}

Zvyagilskaya, Renata A. ^{[8
]}

机构：

[1] Moscow MV Lomonosov State Univ, Belozersky Inst Physicochem Biol, Moscow 119991, Russia

[2] Moscow MV Lomonosov State Univ, Fac Bioengn & Bioinformat, Moscow 119991, Russia

[3] Russian Acad Sci, Frumkin Inst Phys Chem & Electrochem, Moscow 119991, Russia

[4] Russian Acad Sci, NN Semenov Chem Phys Inst, Moscow 117977, Russia

[5] Moscow MV Lomonosov State Univ, Fac Biol, Moscow 119991, Russia

[6] Moscow MV Lomonosov State Univ, Inst Mitoengn, Moscow 119991, Russia

[7] Moscow MV Lomonosov State Univ, Fac Chem, Moscow 119991, Russia

[8] Russian Acad Sci, Bach Inst Biochem, Moscow 119071, Russia

来源：

BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS | 2010年 / 1797卷 / 6-7期

基金：

俄罗斯基础研究基金会;

关键词：

Mitochondria; Reactive oxygen species; SkQ; Antioxidant; Cardiolipin; Fatty acid cycling; Mild uncoupling; BIOMEMBRANE-PRODUCED ENERGY; INTERRUPT EXECUTION; REACTIVE OXYGEN; UNCOUPLING ACTIVITY; ELECTRIC FORM; MITOCHONDRIA; MEMBRANE; TOOLS; ROS; PHOSPHORYLATION;

D O I：

10.1016/j.bbabio.2010.03.015

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

The present state of the art in studies on the mechanisms of antioxidant activities of mitochondria-targeted cationic plastoquinone derivatives (SkQs) is reviewed. Our experiments showed that these compounds can operate as antioxidants in two quite different ways, i.e. (i) by preventing peroxidation of cardiolipin [Antonenko et al., Biochemistry (Moscow) 73 (2008) 1273-1287] and (ii) by fatty acid cycling resulting in mild uncoupling that inhibits the formation of reactive oxygen species (ROS) in mitochondrial State 4 [Severin et al. Proc. Natl. Acad. Sci. USA 107 (2009), 663-668]. The quinol and cationic moieties of SkQ are involved in cases (i) and (ii), respectively. In case (i) SkQH(2) interrupts propagation of chain reactions involved in peroxidation of unsaturated fatty acid residues in cardiolipin, the formed SkQ center dot(-) being reduced back to SkQH(2) by heme b(H) of complex III in an antimycin-sensitive way. Molecular dynamics simulation showed that there are two stable conformations of SkQ1 with the quinol residue localized near peroxyl radicals at C-9 or C-13 of the linoleate residue in cardiolipin. In mechanism (ii), fatty acid cycling mediated by the cationic SkQ moiety is involved. It consists of (a) transmembrane movement of the fatty acid anion/SkQ cation pair and (b) back flows of free SkQ cation and protonated fatty acid. The cycling results in a protonophorous effect that was demonstrated in planar phospholipid membranes and liposomes. In mitochondria, the cycling gives rise to mild uncoupling, thereby decreasing membrane potential and ROS generation coupled to reverse electron transport in the respiratory chain. In yeast cells, dodecyltriphenylphosphonium (C12TPP), the cationic part of SkQ1, induces uncoupling that is mitochondria-targeted since C12TPP is specifically accumulated in mitochondria and increases the H+ conductance of their inner membrane. The conductance of the outer cell membrane is not affected by C12TPP. (C) 2010 Elsevier B.V. All rights reserved.

引用

页码：878 / 889

页数：12

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