title: Functional characterization of a Drosophila mitochondrial uncoupling protein.
abstract: Sequence alignment of conserved signature motifs predicts the existence of the uncoupling protein 5 (UCP5)/brain mitochondrial carrier protein (BMCP1) homologue in Drosophila melanogaster. Here we demonstrate the functional characterization of the Drosophila melanogaster UCP5 protein (DmUCP5) in the heterologous yeast system, the first insect UCP reported to date. We show that physiological levels of DmUCP5 expression are responsible for an increase in state 4 respiration rates and a decrease in mitochondrial membrane potential. Furthermore, similar to UCP1, UCP2, and UCP3, the uncoupling activity of DmUCP5 is augmented by fatty acids and inhibited by the purine nucleotide GDP. Thus, DmUCP5 shares the mechanisms known to regulate the UCPs characterized to date. A lack of growth inhibition observed in DmUCP5 expressing yeast is consistent with the notion that physiological uncoupling has a minimal effect on cell growth. Finally, semiquantitative RT-PCR analysis shows a distinctive pattern of DmUCP5 expression predominantly localized in the adult head, similar to the expression pattern of its mammalian homologues. The conserved regulation of the expression of this gene from mammals to fruit flies suggests a role for UCP5 in the brain.
authors.affiliation: Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, Connecticut, USA. shelfand@neuron.uchc.edu
authors.forename: Yih-Woei C
authors.initials: YW
authors.lastname: Fridell
authors.forename: Adolfo
authors.initials: A
authors.lastname: Sánchez-Blanco
authors.forename: Brian A
authors.initials: BA
authors.lastname: Silvia
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Helfand
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D019069:Cell Respiration / Q000502:physiology; D017931:DNA Primers; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics*; D020869:Gene Expression Profiling; D008564:Membrane Potentials; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics* / Q000378:metabolism; D000071245:Mitochondrial Uncoupling Proteins; D008969:Molecular Sequence Data; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D015003:Yeasts
chemical_list: C497130:Bmcp protein, Drosophila; D017931:DNA Primers; D029721:Drosophila Proteins; D024101:Mitochondrial Proteins; D000071245:Mitochondrial Uncoupling Proteins