title: Interaction of tetraphenylphosphonium and dodecyltriphenylphosphonium with lipid membranes and mitochondria.
abstract: The permeability of a planar lipid membrane (composed of diphytanoylphosphatidylcholine) for tetraphenylphosphonium (TPP) was investigated. The observed level of the diffusion potential generated as a function of the TPP concentration gradient differed from the theoretically expected value, possibly due to proton leakage of the membrane mediated by the traces of fatty acids in the phospholipid forming the membrane. Using the molecular dynamics approach to study movement of TPP and dodecyltriphenylphosphonium (C(12)TPP) with different affinity to the lipid bilayer through a bilayer lipid membrane, it was found that C(12)TPP has a greater affinity to the membrane surface than TPP. However, the two cations have the same activation energy for transmembrane transfer. Interaction of TPP and C(12)TPP with tightly-coupled mitochondria from the yeast Yarrowia lipolytica was also investigated. At low, micromolar concentrations, both cations are "relatively weak, mild uncouplers", do not shunt electron transfer along the respiratory chain, do not disturb (damage) the inner mitochondrial membrane, and profoundly promote the uncoupling effect of fatty acids. At higher concentrations they inhibit respiration in state 3, and at much higher concentrations they induce swelling of mitochondria, possibly due to their detergent action.
authors.affiliation: Bach Institute of Biochemistry, Russian Academy of Sciences, 119071 Moscow, Russia.
authors.forename: T A
authors.initials: TA
authors.lastname: Trendeleva
authors.forename: A G
authors.initials: AG
authors.lastname: Rogov
authors.forename: D A
authors.initials: DA
authors.lastname: Cherepanov
authors.forename: E I
authors.initials: EI
authors.lastname: Sukhanova
authors.forename: T M
authors.initials: TM
authors.lastname: Il'yasova
authors.forename: I I
authors.initials: II
authors.lastname: Severina
authors.forename: R A
authors.initials: RA
authors.lastname: Zvyagilskaya
mesh_terms: D019069:Cell Respiration / Q000187:drug effects; D008051:Lipid Bilayers / Q000737:chemistry* / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism; D008933:Mitochondrial Swelling / Q000187:drug effects; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D009861:Onium Compounds / Q000737:chemistry* / Q000494:pharmacology; D009943:Organophosphorus Compounds / Q000737:chemistry* / Q000494:pharmacology; D014475:Uncoupling Agents / Q000737:chemistry / Q000494:pharmacology; D025062:Yarrowia / Q000166:cytology
chemical_list: D008051:Lipid Bilayers; D024101:Mitochondrial Proteins; D009861:Onium Compounds; D009943:Organophosphorus Compounds; D014475:Uncoupling Agents; C001115:dodecyltriphenylphosphonium; C013289:tetraphenylphosphonium