Penetrating cation/fatty acid anion pair as a mitochondria-targeted protonophore
| Autor: | Fedor F. Severin, Galina A. Korshunova, Antonina V. Pustovidko, Maxim V. Skulachev, Dmitry A. Cherepanov, Nataliya V. Sumbatyan, Mikhail Yu. Vyssokikh, Lev S. Yaguzhinsky, Tatiana I. Rokitskaya, Vladimir P. Skulachev, Elena N. Mokhova, Inna I. Severina, Yury N. Antonenko, Olga V. Markova |
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| Rok vydání: | 2009 |
| Předmět: |
Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone
1 2-Dipalmitoylphosphatidylcholine Plastoquinone Protonophore Phospholipid Mitochondria Liver chemistry.chemical_compound Cytosol Onium Compounds Organophosphorus Compounds Hypothyroidism Cations Neoplasms Animals Humans Obesity Cellular Senescence chemistry.chemical_classification Membrane potential Liposome Multidisciplinary Chemistry Bilayer Fatty Acids Fatty acid Biological Sciences Hydrogen-Ion Concentration Mitochondria Rats Kinetics Biochemistry Mitochondrial Membranes Biophysics Carbonyl cyanide-p-trifluoromethoxyphenylhydrazone Protons Reactive Oxygen Species Cell aging |
| Zdroj: | Proceedings of the National Academy of Sciences. 107:663-668 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.0910216107 |
| Popis: | A unique phenomenon of mitochondria-targeted protonophores is described. It consists in a transmembrane H + -conducting fatty acid cycling mediated by penetrating cations such as 10-(6’-plastoquinonyl)decyltriphenylphosphonium (SkQ1) or dodecyltriphenylphosphonium (C 12 TPP). The phenomenon has been modeled by molecular dynamics and directly proved by experiments on bilayer planar phospholipid membrane, liposomes, isolated mitochondria, and yeast cells. In bilayer planar phospholipid membrane, the concerted action of penetrating cations and fatty acids is found to result in conversion of a pH gradient (ΔpH) to a membrane potential (Δ ψ ) of the Nernstian value (about 60 mV Δ ψ at ΔpH = 1). A hydrophobic cation with localized charge (cetyltrimethylammonium) failed to substitute for hydrophobic cations with delocalized charge. In isolated mitochondria, SkQ1 and C 12 TPP, but not cetyltrimethylammonium, potentiated fatty acid-induced ( i ) uncoupling of respiration and phosphorylation, and ( ii ) inhibition of H 2 O 2 formation. In intact yeast cells, C 12 TPP stimulated respiration regardless of the extracellular pH value, whereas a nontargeted protonophorous uncoupler (trifluoromethoxycarbonylcyanide phenylhydrazone) stimulated respiration at pH 5 but not at pH 3. Hydrophobic penetrating cations might be promising to treat obesity, senescence, and some kinds of cancer that require mitochondrial hyperpolarization. |
| Databáze: | OpenAIRE |
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