title: Htd2p/Yhr067p is a yeast 3-hydroxyacyl-ACP dehydratase essential for mitochondrial function and morphology.
abstract: Among the recently recognized aspects of mitochondrial functions, in yeast as well as humans, is their ability to synthesize fatty acids in a malonyl-CoA dependent manner. We describe here the identification of the 3-hydroxyacyl-ACP dehydratase involved in mitochondrial fatty acid synthesis. A colony-colour-sectoring screen was applied in Saccharomyces cerevisiae in a search for mutants that, when grown on a non-fermentable carbon source, were unable to lose a plasmid that carried a chimeric construct coding for mitochondrially localized bacterial analogue. Our mutants, which are respiratory deficient, lack cytochromes and display abnormal mitochondrial morphology, were found to have a lesion in the yeast YHR067w/RMD12 gene. The Yhr067p is predicted to be a member of the thioesterase/thioester dehydratase-isomerase superfamily enzymes. Hydratase 2 activity in mitochondrial extracts from cells overexpressing YHR067w was increased. These overexpressing cells also display a striking mitochondrial enlargement phenotype. We conclude that YHR067w encodes a novel mitochondrial 3-hydroxyacyl-thioester dehydratase 2 and suggest renaming it HTD2. The mitochondrial phenotypes of the null and overexpression mutants suggest a crucial role of YHR067w in maintenance of mitochondrial respiratory competence and morphology in yeast.
authors.affiliation: Biocenter Oulu, Department of Biochemistry, University of Oulu, FIN-90014 Oulu, Finland.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Kastaniotis
authors.forename: Kaija J
authors.initials: KJ
authors.lastname: Autio
authors.forename: Raija T
authors.initials: RT
authors.lastname: Sormunen
authors.forename: J Kalervo
authors.initials: JK
authors.lastname: Hiltunen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019069:Cell Respiration / Q000235:genetics; D003066:Coenzyme A Ligases / Q000235:genetics / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000235:genetics; D005227:Fatty Acids / Q000096:biosynthesis*; D006801:Humans; D006836:Hydro-Lyases / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure*; D024101:Mitochondrial Proteins; D008969:Molecular Sequence Data; D010641:Phenotype; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment
chemical_list: D004272:DNA, Mitochondrial; D005227:Fatty Acids; D024101:Mitochondrial Proteins; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; C495281:Htd2 protein, S cerevisiae; D006836:Hydro-Lyases; D003066:Coenzyme A Ligases; C090799:FAA2 protein, S cerevisiae