Htd2p/Yhr067p is a yeast 3-hydroxyacyl-ACP dehydratase essential for mitochondrial function and morphology

Mol Microbiol. 2004 Sep;53(5):1407-21. doi: 10.1111/j.1365-2958.2004.04191.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Respiration / genetics
  • Coenzyme A Ligases / genetics
  • Coenzyme A Ligases / metabolism
  • DNA, Mitochondrial / genetics
  • Fatty Acids / biosynthesis*
  • Humans
  • Hydro-Lyases / genetics
  • Hydro-Lyases / metabolism*
  • Mitochondria / metabolism*
  • Mitochondria / ultrastructure*
  • Mitochondrial Proteins
  • Molecular Sequence Data
  • Phenotype
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / enzymology*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Sequence Alignment


  • DNA, Mitochondrial
  • Fatty Acids
  • Mitochondrial Proteins
  • Repressor Proteins
  • Saccharomyces cerevisiae Proteins
  • Htd2 protein, S cerevisiae
  • Hydro-Lyases
  • Coenzyme A Ligases
  • FAA2 protein, S cerevisiae