Electrogenic proton transport across lipid bilayer membranes mediated by cationic derivatives of rhodamine 19: compariso
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ORIGINAL PAPER
Electrogenic proton transport across lipid bilayer membranes mediated by cationic derivatives of rhodamine 19: comparison with anionic protonophores Tatyana I. Rokitskaya • Tatyana M. Ilyasova Inna I. Severina • Yuri N. Antonenko • Vladimir P. Skulachev
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Received: 16 October 2012 / Revised: 24 January 2013 / Accepted: 21 March 2013 / Published online: 5 April 2013 Ó European Biophysical Societies’ Association 2013
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 plastoquinonelacking 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
T. I. Rokitskaya (&) Y. N. Antonenko V. P. Skulachev A. N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow 119992, Russia e-mail: [email protected] T. M. Ilyasova V. P. Skulachev Institute of Mitoengineering, Lomonosov Moscow State University, Vorobyevy Gory 1, Moscow 119991, Russia I. I. Severina Biological Department, Lomonosov Moscow State University, Moscow 119991, Russia V. P. Skulachev Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow 119991, Russia
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. Keywords Bilayer lipid membrane Protonophore Uncoupling activity Dipole potential SkQR1
Introduction Carriers of hydrogen ions (protonophores) have been extensively studied in model membrane systems and serve in biochemistry and cell biology for identification of the role of mitochondria in different physiological processes. They uncouple oxidation and ADP phosphorylation by decreasing the mitochondrial membrane potential and DpH, which also regulate many metabolic pathways, such as, for example, generation of reactive oxygen species (ROS). It has been suggested that protonophores can be used as
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