title: Role of the transmembrane potential in the membrane proton leak.
abstract: The molecular mechanism responsible for the regulation of the mitochondrial membrane proton conductance (G) is not clearly understood. This study investigates the role of the transmembrane potential (DeltaPsim) using planar membranes, reconstituted with purified uncoupling proteins (UCP1 and UCP2) and/or unsaturated FA. We show that high DeltaPsim (similar to DeltaPsim in mitochondrial State IV) significantly activates the protonophoric function of UCPs in the presence of FA. The proton conductance increases nonlinearly with DeltaPsim. The application of DeltaPsim up to 220 mV leads to the overriding of the protein inhibition at a constant ATP concentration. Both, the exposure of FA-containing bilayers to high DeltaPsim and the increase of FA membrane concentration bring about the significant exponential Gm increase, implying the contribution of FA in proton leak. Quantitative analysis of the energy barrier for the transport of FA anions in the presence and absence of protein suggests that FA- remain exposed to membrane lipids while crossing the UCP-containing membrane. We believe this study shows that UCPs and FA decrease DeltaPsim more effectively if it is sufficiently high. Thus, the tight regulation of proton conductance and/or FA concentration by DeltaPsim may be key in mitochondrial respiration and metabolism.
authors.affiliation: Department of Biomedical Sciences, University of Veterinary Medicine, Vienna, Austria.
authors.forename: Anne
authors.initials: A
authors.lastname: Rupprecht
authors.forename: Elena A
authors.initials: EA
authors.lastname: Sokolenko
authors.forename: Valeri
authors.initials: V
authors.lastname: Beck
authors.forename: Olaf
authors.initials: O
authors.lastname: Ninnemann
authors.forename: Martin
authors.initials: M
authors.lastname: Jaburek
authors.forename: Thorsten
authors.initials: T
authors.lastname: Trimbuch
authors.forename: Sergey S
authors.initials: SS
authors.lastname: Klishin
authors.forename: Petr
authors.initials: P
authors.lastname: Jezek
authors.forename: Vladimir P
authors.initials: VP
authors.lastname: Skulachev
authors.forename: Elena E
authors.initials: EE
authors.lastname: Pohl
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D004553:Electric Conductivity; D005227:Fatty Acids / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D007473:Ion Channels / Q000302:isolation & purification / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000302:isolation & purification / Q000378:metabolism; D017711:Nonlinear Dynamics; D011522:Protons; D000071256:Uncoupling Protein 1; D000071246:Uncoupling Protein 2
chemical_list: D005227:Fatty Acids; D007473:Ion Channels; D024101:Mitochondrial Proteins; D011522:Protons; C000604371:UCP1 protein, human; C000604389:UCP2 protein, human; C000604372:Ucp1 protein, mouse; C000604390:Ucp2 protein, mouse; D000071256:Uncoupling Protein 1; D000071246:Uncoupling Protein 2; D000255:Adenosine Triphosphate
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