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Electrogenic proton transport across lipid bilayer membranes mediated by cationic derivatives of rhodamine 19: comparison with anionic protonophores

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Abstract

Protonophores can be considered as candidates for anti-obesity drugs and tools to prevent excessive reactive oxygen species production in mitochondria by means of a limited decrease in the mitochondrial potential. Experimentally used protonophores are weak acids that can carry protons across a membrane in a neutral (protonated) form, and they come back in an anionic (deprotonated) form. A cationic derivative of rhodamine 19 and plastoquinone (SkQR1) was recently shown to possess uncoupling activity in mitochondria and in intact cells. In this article, we studied the mechanism of action of SkQR1 and its plastoquinone-lacking analog (C12R1) on a planar bilayer lipid membrane by applying voltage jumps. The steady-state current was proportional to the C12R1 concentration in a manner as if the monomeric form of the carrier were operative. As predicted by the carrier model, at high pH, when rhodamines were mainly deprotonated, the current changed immediately following a jump in the applied potential and then remained constant. By contrast, at low pH, the current relaxed from an initially high value to a lower value since the protonated carrier cations were redistributed in the membrane. An inverse pH dependence was revealed with the anionic protonophore CCCP. The dependence of the SkQR1 protonophorous activity on voltage exhibited an increase at high voltages, an effect that might facilitate mild (self-limited) uncoupling of mitochondria.

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Acknowledgments

The authors thank Dr. Elena Kotova for valuable comments. This work was supported in part by the Russian Foundation for Basic Research grant 12-04-00199 and the Institute of Mitoengineering, Lomonosov Moscow State University.

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Authors and Affiliations

  1. A. N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119992, Russia

    Tatyana I. Rokitskaya, Yuri N. Antonenko & Vladimir P. Skulachev

  2. Institute of Mitoengineering, Lomonosov Moscow State University, Vorobyevy Gory 1, Moscow, 119991, Russia

    Tatyana M. Ilyasova & Vladimir P. Skulachev

  3. Biological Department, Lomonosov Moscow State University, Moscow, 119991, Russia

    Inna I. Severina

  4. Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, 119991, Russia

    Vladimir P. Skulachev

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  1. Tatyana I. Rokitskaya
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  2. Tatyana M. Ilyasova
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  3. Inna I. Severina
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  4. Yuri N. Antonenko
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  5. Vladimir P. Skulachev
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Correspondence to Tatyana I. Rokitskaya.

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Rokitskaya, T.I., Ilyasova, T.M., Severina, I.I. et al. Electrogenic proton transport across lipid bilayer membranes mediated by cationic derivatives of rhodamine 19: comparison with anionic protonophores. Eur Biophys J 42, 477–485 (2013). https://doi.org/10.1007/s00249-013-0898-9

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  • DOI: https://doi.org/10.1007/s00249-013-0898-9

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