SkQ3: The new member of the class of membranotropic uncouplers

  • S. A. Eremeev
  • K. A. Motovilov
  • E. M. Volkov
  • L. S. YaguzhinskyEmail author


In our previous studies we have described the non-equilibrium binding of hydrogen ions to the membranes upon induction of transmembrane proton flux in the model system (BLM) and in mitochondria. In 2009 the investigation program aimed to find uncouplers selectively interacting with the non-equilibrium bound protons was started. This study is devoted to a new representative of this class of uncouplers. The effect of respiratory stimulation evoked by this compound can be suppressed by 50–90% through the elimination of non-equilibrium fraction of protons associated with the outer side of the inner mitochondrial membrane. The peculiarity of this compound results from its belonging to the class of quinones with a high affinity to lipid membranes. It becomes a weak acid (hydroquinone) only after reduction. The formation of hydroquinone in the mitochondria determines the observed effect of respiratory stimulation. Thus, the artificial induction of interaction between redox-reactions and reactions of proton association and dissociation occurring on the surface of the inner mitochondrial membrane was demonstrated for the first time.


mitochondria membranotropic uncouplers SkQ non-equilibrium proton binding on the membrane 





[10-(2,4,5-trimethyl-3,6-dioxycyclohexane-1,4-diene-1-il)decyl]triphenylphosphonium chloride


non-equilibrium membrane bounding proteins


[10(2,4,5-trimethyl-3,6-dioxycyclo-hexa-1,4-diene-1-il)decyl]triphenylphosphonium chloride






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  1. 1.
    Drachev L.A., Kaulen A.D., Skulachev V.P. 1984. Correlation of photochemical cycle, H+ release and uptake, and electric events in bacteriorhodopsin. FEBS Lett. 178, 331–335.CrossRefGoogle Scholar
  2. 2.
    Antonenko Y.N., Kovbasnjuk O.N., Yaguzhinsky L.S. 1993. Evidence in favor of the existence of a kinetic barrier for proton transfer from a surface of bilayer phospholipid membrane to bulk water. Biochim. Biophys. Acta. 1150, 45–50.PubMedCrossRefGoogle Scholar
  3. 3.
    Krasinskaya I.P., Marshansky V.N., Dragunova S.F., Yaguzhinsky L.S. 1984. Relationships of respiratory chain and ATP-synthetase in energized mitochondria. FEBS Lett. 167(1), 176–180.PubMedCrossRefGoogle Scholar
  4. 4.
    Murugova T.N., Gordeliy V.I., Kuklin A.I., Solodovnikova I.M., Yaguzhinsky L.S. 2007 The structure of macromolecular compoumds. Register three-dimensional ordered structures in intact mitochondria using the method of small-angle neutron scattering. Kristallografia (Rus.). 52(3), 545–548.Google Scholar
  5. 5.
    Heberle J., Riesle J., Thiedemann G., Oesterhelt D., Dencher N.A. 1994. Proton migration along the membrane surface and retarded surface to bulk transfer. Nature. 370, 379–382.PubMedCrossRefGoogle Scholar
  6. 6.
    Serowy S., Saparov S.M., Antonenko Y.N., Kozlovsky W., Hagen V., Pohl P. 2003. Structural proton diffusion along lipid bilayers. Biophys. J. 84, 1031–1037.PubMedCrossRefGoogle Scholar
  7. 7.
    Yaguzhinsky L.S., Yurkov V.I., Krasinskaya I.P. 2006. On the localized coupling of respiration and phosphorylation in mitochondria. Biochim. Biophys. Acta. 1757, 408–414.PubMedCrossRefGoogle Scholar
  8. 8.
    Yurkov V.I., Fadeeva M.S., Yaguzhinsky L.S. 2005. Proton transfer through the membrane-water interfaces in uncoupled mitochondria. Biochemistry (Moscow). 70, 195–199.CrossRefGoogle Scholar
  9. 9.
    Motovilov K.A., Yurkov V.I., Volkov E.M., Yaguzhinsky L.S. 2009. Properties and new methods of nonequilibrium membrane bounded proton fraction research under conditions of proton pump activation. Biochemistry (Moscow) Suppl. Ser. A: Membrane Cell Biol. 26(5), 408–418.Google Scholar
  10. 10.
    Kramer R. 1998. Mitochondrial carrier proteins can reversibly change their transport mode: The cases of the aspartate/glutamate and the phosphate carrier. Exp. Physiol. 83, 259–265.PubMedGoogle Scholar
  11. 11.
    Kargin V.I., Motovilov K.A., Vyssokikh M.Y., Yaguzhinsky L.S. 2008. Interaction of positively charged ubiquinone analog (MitoQ10) with DT-diaphorase from liver mitochondria. Biochemistry (Moscow) Suppl. Ser. A: Membrane Cell Biol. 2, 33–39.Google Scholar
  12. 12.
    Eremeyev S.A., Kargin V.I., Motoilov K.A., Tashlistky V.N., Markov V.Y., Korshunova G.A., Sumbatyan N.V., Vissokikh M.Y., Yaguzhinsky L.S. 2009. Molecular mechanisms of transformation of SkQ mitotropic quinones and the search for new approaches to creation of selective free radical traps. Biochemestry (Moscow). 74(10), 1368–1379.Google Scholar
  13. 13.
    Johnson D., Lardy H. 1967. Isolation of liver or kidney mitochondria. Meth. Enzymol. 10, 94–96.CrossRefGoogle Scholar
  14. 14.
    Kotlyar A.B., Vinogradov A.D. 1984. Interaction of the membrane-bound succinate dehydrogenase with substrate and competitive inhibitors. Biochim. Biophys. Acta. 784, 24–34.PubMedCrossRefGoogle Scholar
  15. 15.
    Solodovnikova I.M., Yurkov V.I., Ton’shin A.A., Yaguzhinskii L.S. 2004. Local coupling between respiration and phosphorylation in rat liver mitochondria. Biophysics. 49, 42–51.Google Scholar
  16. 16.
    Kozlova M.V., Gramadskii K.B., Solodovnikova I.M., Krasinskaya I.P., Vinogradov A.V., Yaguzhinskii L.S. 2003. Detection and functional role of local H+-activity gradients on the inner mitochondrial membrane labeled with covalently bound pH probe. Biophysics. 48, 443–452.Google Scholar

Copyright information

© Pleiades Publishing, Ltd. 2011

Authors and Affiliations

  • S. A. Eremeev
    • 1
  • K. A. Motovilov
    • 2
    • 3
  • E. M. Volkov
    • 3
  • L. S. Yaguzhinsky
    • 2
    • 3
    • 4
    Email author
  1. 1.Faculty of Bioengineering and BioinformaticsMoscow Lomonosov State UniversityMoscowRussia
  2. 2.Research and Education Center BioNanoPhysicsMoscow Institute of Physics and Technology (State University)Dolgoprudny, Moscow oblastRussia
  3. 3.Belozersky Research Institute of Physico-chemical BiologyMoscow Lomonosov State UniversityMoscowRussia
  4. 4.Institute of MitoengineeringMoscow Lomonosov State UniversityMoscowRussia

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