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PMID: 20409469 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Role of the transmembrane potential in the membrane proton leak.

Biophysical journal ·Vol. 98 ·No. 8 ·2010-04-21 ·Pages 1503-11

Rupprecht A, Sokolenko EA, Beck V, Ninnemann O, Jaburek M, Trimbuch T, Klishin SS, Jezek P, Skulachev VP, Pohl EE

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.

MeSH Terms
Adenosine Triphosphate/pharmacology Animals Electric Conductivity Fatty Acids/pharmacology Humans Hydrogen-Ion Concentration/drug effects Ion Channels/isolation & purification,metabolism Membrane Potential, Mitochondrial/drug effects,physiology Mice Mitochondrial Membranes/drug effects,metabolism Mitochondrial Proteins/isolation & purification,metabolism Nonlinear Dynamics Protons Uncoupling Protein 1 Uncoupling Protein 2
Chemicals
Fatty Acids Ion Channels Mitochondrial Proteins Protons UCP1 protein, human UCP2 protein, human Ucp1 protein, mouse Ucp2 protein, mouse Uncoupling Protein 1 Uncoupling Protein 2 Adenosine Triphosphate
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Rupprecht Anne
Department of Biomedical Sciences, University of Veterinary Medicine, Vienna, Austria.
Sokolenko Elena A
Beck Valeri
Ninnemann Olaf
Jaburek Martin
Trimbuch Thorsten
Klishin Sergey S
Jezek Petr
Skulachev Vladimir P
Pohl Elena E
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Article Info
Journal
Biophysical journal
Abbr.
Biophys J
ISSN
1542-0086
DOI
10.1016/j.bpj.2009.12.4301
Published
2010-04-21
Pages
1503-11
Language
English
Region
United States
NLM ID
0370626
PMCID
PMC2856137
Subset
IM
External Links
PubMed source DOI: 10.1016/j.bpj.2009.12.4301 PMC Full Text View journal details
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