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Penetrating Cations Enhance Uncoupling Activity of Anionic Protonophores in Mitochondria

Protonophorous uncouplers causing a partial decrease in mitochondrial membrane potential are promising candidates for therapeutic applications. Here we showed that hydrophobic penetrating cations specifically targeted to mitochondria in a membrane potential-driven fashion increased proton-translocat...

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Autores principales: Antonenko, Yuri N., Khailova, Ljudmila S., Knorre, Dmitry A., Markova, Olga V., Rokitskaya, Tatyana I., Ilyasova, Tatyana M., Severina, Inna I., Kotova, Elena A., Karavaeva, Yulia E., Prikhodko, Anastasia S., Severin, Fedor F., Skulachev, Vladimir P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3633956/
https://www.ncbi.nlm.nih.gov/pubmed/23626747
http://dx.doi.org/10.1371/journal.pone.0061902
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author Antonenko, Yuri N.
Khailova, Ljudmila S.
Knorre, Dmitry A.
Markova, Olga V.
Rokitskaya, Tatyana I.
Ilyasova, Tatyana M.
Severina, Inna I.
Kotova, Elena A.
Karavaeva, Yulia E.
Prikhodko, Anastasia S.
Severin, Fedor F.
Skulachev, Vladimir P.
author_facet Antonenko, Yuri N.
Khailova, Ljudmila S.
Knorre, Dmitry A.
Markova, Olga V.
Rokitskaya, Tatyana I.
Ilyasova, Tatyana M.
Severina, Inna I.
Kotova, Elena A.
Karavaeva, Yulia E.
Prikhodko, Anastasia S.
Severin, Fedor F.
Skulachev, Vladimir P.
author_sort Antonenko, Yuri N.
collection PubMed
description Protonophorous uncouplers causing a partial decrease in mitochondrial membrane potential are promising candidates for therapeutic applications. Here we showed that hydrophobic penetrating cations specifically targeted to mitochondria in a membrane potential-driven fashion increased proton-translocating activity of the anionic uncouplers 2,4-dinitrophenol (DNP) and carbonylcyanide-p-trifluorophenylhydrazone (FCCP). In planar bilayer lipid membranes (BLM) separating two compartments with different pH values, DNP-mediated diffusion potential of H(+) ions was enhanced in the presence of dodecyltriphenylphosphonium cation (C(12)TPP). The mitochondria-targeted penetrating cations strongly increased DNP- and carbonylcyanide m-chlorophenylhydrazone (CCCP)-mediated steady-state current through BLM when a transmembrane electrical potential difference was applied. Carboxyfluorescein efflux from liposomes initiated by the plastoquinone-containing penetrating cation SkQ1 was inhibited by both DNP and FCCP. Formation of complexes between the cation and CCCP was observed spectophotometrically. In contrast to the less hydrophobic tetraphenylphosphonium cation (TPP), SkQ1 and C(12)TPP promoted the uncoupling action of DNP and FCCP on isolated mitochondria. C(12)TPP and FCCP exhibited a synergistic effect decreasing the membrane potential of mitochondria in yeast cells. The stimulating action of penetrating cations on the protonophore-mediated uncoupling is assumed to be useful for medical applications of low (non-toxic) concentrations of protonophores.
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spelling pubmed-36339562013-04-26 Penetrating Cations Enhance Uncoupling Activity of Anionic Protonophores in Mitochondria Antonenko, Yuri N. Khailova, Ljudmila S. Knorre, Dmitry A. Markova, Olga V. Rokitskaya, Tatyana I. Ilyasova, Tatyana M. Severina, Inna I. Kotova, Elena A. Karavaeva, Yulia E. Prikhodko, Anastasia S. Severin, Fedor F. Skulachev, Vladimir P. PLoS One Research Article Protonophorous uncouplers causing a partial decrease in mitochondrial membrane potential are promising candidates for therapeutic applications. Here we showed that hydrophobic penetrating cations specifically targeted to mitochondria in a membrane potential-driven fashion increased proton-translocating activity of the anionic uncouplers 2,4-dinitrophenol (DNP) and carbonylcyanide-p-trifluorophenylhydrazone (FCCP). In planar bilayer lipid membranes (BLM) separating two compartments with different pH values, DNP-mediated diffusion potential of H(+) ions was enhanced in the presence of dodecyltriphenylphosphonium cation (C(12)TPP). The mitochondria-targeted penetrating cations strongly increased DNP- and carbonylcyanide m-chlorophenylhydrazone (CCCP)-mediated steady-state current through BLM when a transmembrane electrical potential difference was applied. Carboxyfluorescein efflux from liposomes initiated by the plastoquinone-containing penetrating cation SkQ1 was inhibited by both DNP and FCCP. Formation of complexes between the cation and CCCP was observed spectophotometrically. In contrast to the less hydrophobic tetraphenylphosphonium cation (TPP), SkQ1 and C(12)TPP promoted the uncoupling action of DNP and FCCP on isolated mitochondria. C(12)TPP and FCCP exhibited a synergistic effect decreasing the membrane potential of mitochondria in yeast cells. The stimulating action of penetrating cations on the protonophore-mediated uncoupling is assumed to be useful for medical applications of low (non-toxic) concentrations of protonophores. Public Library of Science 2013-04-23 /pmc/articles/PMC3633956/ /pubmed/23626747 http://dx.doi.org/10.1371/journal.pone.0061902 Text en © 2013 Antonenko et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Antonenko, Yuri N.
Khailova, Ljudmila S.
Knorre, Dmitry A.
Markova, Olga V.
Rokitskaya, Tatyana I.
Ilyasova, Tatyana M.
Severina, Inna I.
Kotova, Elena A.
Karavaeva, Yulia E.
Prikhodko, Anastasia S.
Severin, Fedor F.
Skulachev, Vladimir P.
Penetrating Cations Enhance Uncoupling Activity of Anionic Protonophores in Mitochondria
title Penetrating Cations Enhance Uncoupling Activity of Anionic Protonophores in Mitochondria
title_full Penetrating Cations Enhance Uncoupling Activity of Anionic Protonophores in Mitochondria
title_fullStr Penetrating Cations Enhance Uncoupling Activity of Anionic Protonophores in Mitochondria
title_full_unstemmed Penetrating Cations Enhance Uncoupling Activity of Anionic Protonophores in Mitochondria
title_short Penetrating Cations Enhance Uncoupling Activity of Anionic Protonophores in Mitochondria
title_sort penetrating cations enhance uncoupling activity of anionic protonophores in mitochondria
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3633956/
https://www.ncbi.nlm.nih.gov/pubmed/23626747
http://dx.doi.org/10.1371/journal.pone.0061902
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