The alternative pathway of glutathione degradation is mediated by a novel protein complex involving three new genes in Saccharomyces cerevisiae

Genetics. 2007 Mar;175(3):1137-51. doi: 10.1534/genetics.106.066944. Epub 2006 Dec 18.


Glutathione (GSH), L-gamma-glutamyl-L-cysteinyl-glycine, is the major low-molecular-weight thiol compound present in almost all eukaryotic cells. GSH degradation proceeds through the gamma-glutamyl cycle that is initiated, in all organisms, by the action of gamma-glutamyl transpeptidase. A novel pathway for the degradation of GSH that requires the participation of three previously uncharacterized genes is described in the yeast Saccharomyces cerevisiae. These genes have been named DUG1 (YFR044c), DUG2 (YBR281c), and DUG3 (YNL191w) (defective in utilization of glutathione). Although dipeptides and tripeptides with a normal peptide bond such as cys-gly or glu-cys-gly required the presence of only a functional DUG1 gene that encoded a protein belonging to the M20A metallohydrolase family, the presence of an unusual peptide bond such as in the dipeptide, gamma-glu-cys, or in GSH, required the participation of the DUG2 and DUG3 gene products as well. The DUG2 gene encodes a protein with a peptidase domain and a large WD40 repeat region, while the DUG3 gene encoded a protein with a glutamine amidotransferase domain. The Dug1p, Dug2p, and Dug3p proteins were found to form a degradosomal complex through Dug1p-Dug2p and Dug2p-Dug3p interactions. A model is proposed for the functioning of the Dug1p/Dug2p/Dug3p proteins as a specific GSH degradosomal complex.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carbon-Nitrogen Ligases / genetics
  • Carbon-Nitrogen Ligases / metabolism*
  • Cloning, Molecular
  • Dipeptidases
  • Genetic Complementation Test
  • Glutathione / metabolism*
  • Hydrolases / genetics
  • Hydrolases / metabolism
  • Immunoprecipitation
  • Microscopy, Fluorescence
  • Models, Biological*
  • Multiprotein Complexes / genetics*
  • Multiprotein Complexes / metabolism*
  • Peptide Hydrolases / genetics
  • Peptide Hydrolases / metabolism*
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Transaminases / genetics
  • Transaminases / metabolism
  • Two-Hybrid System Techniques


  • Multiprotein Complexes
  • Saccharomyces cerevisiae Proteins
  • Transaminases
  • glutamine-pyruvate aminotransferase
  • Hydrolases
  • DUG2 protein, S cerevisiae
  • Peptide Hydrolases
  • DUG1 protein, S cerevisiae
  • Dipeptidases
  • Carbon-Nitrogen Ligases
  • DUG3 protein, S cerevisiae
  • Glutathione