SkQ3: The new member of the class of membranotropic uncouplers

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

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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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Keywords

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