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SkQ3: The new member of the class of membranotropic uncouplers

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Biochemistry (Moscow) Supplement Series A: Membrane and Cell Biology Aims and scope

Abstract

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.

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Abbreviations

TCP-C15:

2,4,6,-trichloro-3-pentadecylphenol

SkQ3:

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

NMBP:

non-equilibrium membrane bounding proteins

SkQ3H2:

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

PCP:

pentachlorophenol

NEM:

N-ethylmaleimide

References

  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.

    Article  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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. 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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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. 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. Johnson D., Lardy H. 1967. Isolation of liver or kidney mitochondria. Meth. Enzymol. 10, 94–96.

    Article  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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. 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.

    CAS  Google Scholar 

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Correspondence to L. S. Yaguzhinsky.

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Original Russian Text © S.A. Eremeev, K.A. Motovilov, E.M. Volkov, L.S. Yaguzhinsky, 2011, published in Biologicheskie Membrany, 2011, Vol. 28, No. 5, pp. 339–344.

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Eremeev, S.A., Motovilov, K.A., Volkov, E.M. et al. SkQ3: The new member of the class of membranotropic uncouplers. Biochem. Moscow Suppl. Ser. A 5, 310–315 (2011). https://doi.org/10.1134/S1990747811050047

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  • DOI: https://doi.org/10.1134/S1990747811050047

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