title: Fatty acid activation of the uncoupling proteins requires the presence of the central matrix loop from UCP1.
abstract: Noradrenaline signals the initiation of brown fat thermogenesis and the fatty acids liberated by the hormone-stimulated lipolysis act as second messengers to activate the uncoupling protein UCP1. UCP1 is a mitochondrial transporter that catalyses the re-entry of protons to the mitochondrial matrix thus allowing a regulated discharge of the proton gradient. The high affinity of UCP1 for fatty acids is a distinct feature of this uncoupling protein. The uncoupling proteins belong to a protein superfamily formed by the mitochondrial metabolite carriers. Members of this family present a tripartite structure where a domain containing two transmembrane helices, linked by a long hydrophilic loop, is repeated three times. Using protein chimeras, where the repeats had been swapped between UCP1 and UCP3, it has been shown that the central third of UCP1 is necessary and sufficient for the response of the protein to fatty acids. We have extended those studies and in the present report we have generated protein chimeras where different regions of the second repeat of UCP1 have been sequentially replaced with their UCP2 counterparts. The resulting chimeras present a progressive degradation of the characteristic bioenergetic properties of UCP1. We demonstrate that the presence of the second matrix loop is necessary for the high affinity activation of UCP1 by fatty acids.
authors.affiliation: Centro de Investigaciones Biológicas, CSIC, Ramiro de Maeztu 9, 28040 Madrid, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Jiménez-Jiménez
authors.forename: Amalia
authors.initials: A
authors.lastname: Ledesma
authors.forename: Pilar
authors.initials: P
authors.lastname: Zaragoza
authors.forename: M Mar
authors.initials: MM
authors.lastname: González-Barroso
authors.forename: Eduardo
authors.initials: E
authors.lastname: Rial
mesh_terms: D000818:Animals; D004734:Energy Metabolism; D005227:Fatty Acids / Q000378:metabolism*; D007473:Ion Channels / Q000378:metabolism*; D051379:Mice; D024101:Mitochondrial Proteins / Q000378:metabolism*; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D000071256:Uncoupling Protein 1; D000071246:Uncoupling Protein 2
chemical_list: D005227:Fatty Acids; D007473:Ion Channels; D024101:Mitochondrial Proteins; D011994:Recombinant Proteins; C000604372:Ucp1 protein, mouse; C000604373:Ucp1 protein, rat; C000604390:Ucp2 protein, mouse; C000604391:Ucp2 protein, rat; D000071256:Uncoupling Protein 1; D000071246:Uncoupling Protein 2