Efficiency of mitochondrial uncoupling by modified butyltriphenylphosphonium cations and fatty acids correlates with lipophilicity of cations: Protonophoric vs leakage mechanisms |
| |
| Affiliation: | 1. Institute of Environmental, Chemical and Pharmaceutical Sciences, Federal University of São Paulo, 09972-270 São Paulo, Brazil;2. Division of Dasonomy, Forestry Institute, 02377-000 São Paulo, Brazil;3. Center for Natural and Human Sciences, Federal University of ABC, 09210-180 São Paulo, Brazil;4. Organic Contaminants Nucleus - Contaminants Center, Adolfo Lutz Institute, 01246-902 São Paulo, Brazil;5. Center for Parasitology and Mycology, Adolfo Lutz Institute, 01246-902 São Paulo, Brazil;1. Department of Chemistry, Graduate School of Science, Osaka University, Toyonaka, Osaka 560-0043, Japan;2. Department of Chemistry, De La Salle University, 2401 Taft Avenue, Manila 0922, Philippines;3. Department of Chemistry and Biotechnology, Graduate School of Engineering, Tottori University, 4-101 Koyama-cho Minami, Tottori 680-8552, Japan;4. Forefront Research Centre for Fundamental Science, Graduate School of Science, Osaka University, Toyonaka, Osaka 560-0043, Japan |
| |
| Abstract: | In order to determine the share of protonophoric activity in the uncoupling action of lipophilic cations a number of analogues of butyltriphenylphosphonium with substitutions in phenyl rings (C4TPP-X) were studied on isolated rat liver mitochondria and model lipid membranes. An increase in the rate of respiration and a decrease in the membrane potential of isolated mitochondria were observed for all the studied cations, the efficiency of these processes was significantly enhanced in the presence of fatty acids and correlated with the octanol-water partition coefficient of the cations. The ability of C4TPP-X cations to induce proton transport across the lipid membrane of liposomes loaded with a pH-sensitive fluorescent dye increased also with their lipophilicity and depended on the presence of palmitic acid in the liposome membrane. Of all the cations, only butyl[tri(3,5-dimethylphenyl)]phosphonium (C4TPP-diMe) was able to induce proton transport by the mechanism of formation of a cation-fatty acid ion pair on planar bilayer lipid membranes and liposomes. The rate of oxygen consumption by mitochondria in the presence of C4TPP-diMe increased to the maximum values corresponding to conventional uncouplers; for all other cations the maximum uncoupling rates were significantly lower. We assume that the studied cations of the C4TPP-X series, with the exception of C4TPP-diMe at low concentrations, cause nonspecific leak of ions through lipid model and biological membranes which is significantly enhanced in the presence of fatty acids. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
