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Protective Effects of Mitochondria-Targeted Antioxidant SkQ in Aqueous and Lipid Membrane Environments

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Abstract

The antioxidant activity of mitochondria-targeted small molecules, SkQ1 and MitoQ (conjugates of a lipophilic decyltriphenylphosphonium cation with an antioxidant moiety of a plastoquinone and ubiquinone, respectively), was studied in aqueous solution and in a lipid environment, i.e., micelles, liposomes and planar bilayer lipid membranes. Reactive oxygen species (ROS) were generated by azo initiators or ferrous ions with or without tert-butyl-hydroperoxide (t-BOOH). Chemiluminescence, fluorescence, oxygen consumption and inactivation of gramicidin peptide channels were measured to detect antioxidant activity. In all of the systems studied, SkQ1 was shown to effectively scavenge ROS. The scavenging was inherent to the reduced form of the quinone (SkQ1H2). In the majority of the above model systems, SkQ1 exhibited higher antioxidant activity than MitoQ. It is concluded that SkQ1H2 operates as a ROS scavenger in both aqueous and lipid environments, being effective at preventing ROS-induced damage to membrane lipids as well as membrane-embedded peptides.

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Abbreviations

MitoQ:

10-(6′-Ubiquinonyl)decyltriphenylphosphonium

SkQ1:

10-(6′-Plastoquinonyl)decyltriphenylphosphonium

CoQ1:

Ubiquinone-1

BLM:

Bilayer lipid membrane

ROS:

Reactive oxygen species

ML:

Methyl ester of linoleate

AAPH:

2,2′-Azobis(2-amidinopropane)dihydrochloride

AlPcS3:

Aluminum phthalocyanine trisulfonate

BR:

Rose bengal

MB:

Methylene blue

DPhPC:

Diphytanoylglycerophosphocholine

DPhPG:

Diphytanoylphosphatidylglycerol

TBARS:

Thiobarbituric acid-reactive species

t-BOOH:

Tert-butyl-hydroperoxide

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Acknowledgements

The authors are grateful to Dr. V. Z. Lankin for helpful discussions. This work was supported by Russian Foundation for Basic Research grants 06-04-48523 (to Y. N. A.) and SKOLI NSH-5952.2006.4 (to V. P. S.).

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Authors and Affiliations

  1. A. N. Belozersky Institute of Physico-Chemical Biology, Moscow State University, 119991, Moscow, Russian Federation

    Y. N. Antonenko, A. A. Pashkovskaya, T. I. Rokitskaya, E. A. Kotova, A. A. Zaspa, B. V. Chernyak & V. P. Skulachev

  2. Mitotechnology LLC, Moscow, Russian Federation

    Y. N. Antonenko, V. A. Roginsky, A. A. Pashkovskaya, T. I. Rokitskaya, B. V. Chernyak & V. P. Skulachev

  3. N. N. Semenov Institute of Chemical Physics, Russian Academy of Sciences, 117977, Moscow, Russian Federation

    V. A. Roginsky

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  1. Y. N. Antonenko
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  4. T. I. Rokitskaya
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Correspondence to Y. N. Antonenko.

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Antonenko, Y.N., Roginsky, V.A., Pashkovskaya, A.A. et al. Protective Effects of Mitochondria-Targeted Antioxidant SkQ in Aqueous and Lipid Membrane Environments. J Membrane Biol 222, 141–149 (2008). https://doi.org/10.1007/s00232-008-9108-6

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  • DOI: https://doi.org/10.1007/s00232-008-9108-6

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