title: Synergy of fatty acid and reactive alkenal activation of proton conductance through uncoupling protein 1 in mitochondria.
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.
authors.affiliation: MRC Dunn Human Nutrition Unit, Hills Road, Cambridge CB2 2XY, UK.
authors.forename: Telma C
authors.initials: TC
authors.lastname: Esteves
authors.forename: Nadeene
authors.initials: N
authors.lastname: Parker
authors.forename: Martin D
authors.initials: MD
authors.lastname: Brand
mesh_terms: D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism; D000447:Aldehydes / Q000494:pharmacology*; D000475:Alkenes / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002417:Cattle; D004553:Electric Conductivity; D005227:Fatty Acids / Q000494:pharmacology*; D007473:Ion Channels; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D024101:Mitochondrial Proteins; D000073878:Palm Oil; D010938:Plant Oils / Q000737:chemistry; D011485:Protein Binding; D011522:Protons; D051381:Rats; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000378:metabolism; D000071256:Uncoupling Protein 1
chemical_list: D000447:Aldehydes; D000475:Alkenes; D002352:Carrier Proteins; D005227:Fatty Acids; D007473:Ion Channels; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D010938:Plant Oils; D011522:Protons; C000604371:UCP1 protein, human; C000604372:Ucp1 protein, mouse; C000604373:Ucp1 protein, rat; D000071256:Uncoupling Protein 1; D012710:Serum Albumin, Bovine; D000073878:Palm Oil; C027576:4-hydroxy-2-nonenal