Synergy of fatty acid and reactive alkenal activation of proton conductance through uncoupling protein 1 in mitochondria.

TitleSynergy of fatty acid and reactive alkenal activation of proton conductance through uncoupling protein 1 in mitochondria.
Publication TypeJournal Article
Year of Publication2006
AuthorsEsteves, TC, Parker, N, Brand, MD
JournalBiochem J
Volume395
Issue3
Pagination619-28
Date Published2006 May 01
ISSN1470-8728
KeywordsAdipose Tissue, Brown, Aldehydes, Alkenes, Animals, Carrier Proteins, Cattle, Electric Conductivity, Fatty Acids, Ion Channels, Kinetics, Membrane Potentials, Membrane Proteins, Mice, Mitochondria, Mitochondrial Proteins, Palm Oil, Plant Oils, Protein Binding, Protons, Rats, Saccharomyces cerevisiae, Serum Albumin, Bovine, Uncoupling Protein 1
Abstract

The kinetics of proton transport through mammalian UCP1 (uncoupling protein 1) expressed in yeast mitochondria were measured. There was little or no UCP1 activity in the absence of added palmitate, but significant activity in its presence. The activator 4-HNE (4-hydroxy-2-nonenal) had little effect when added alone, but significantly enhanced proton conductance in the presence of added palmitate. Activation of the proton conductance of UCP1 was synergistic: proton conductance in the presence of both palmitate and 4-HNE was significantly greater than the sum of the individual effects. Mitochondria from control yeast transformed with empty vector showed no such synergy, showing that synergy is a property of UCP1. Activation by the 4-HNE analogue trans-cinnamate showed essentially the same characteristics as activation by 4-HNE. Mitochondria from brown adipose tissue also showed synergistic activation of GDP-sensitive proton conductance by palmitate and 4-HNE. These results show that reactive alkenals activate the proton conductance of UCP1 more strongly when fatty acids are also added, with implications for both mechanistic and physiological models of UCP1 activation.

DOI10.1042/BJ20052004
Alternate JournalBiochem. J.
Citation Key10.1042/BJ20052004
PubMed ID16451125
PubMed Central IDPMC1462701
Grant ListMC_U105663137 / / Medical Research Council / United Kingdom