The thiol oxidant dipyridyl disulfide can supply the PDI-Ero1p pathway with additional oxidative equivalents.
Membrane-permeant oxidants have become a standard tool for studying eukaryotic organisms because they affect the redox state and the redox regulation of different compartments. The ero1-1 mutant is temperature sensitive (37 degrees C) and cannot grow under anaerobic conditions. Low micromolar concentrations of the specific thiol-oxidant dipyridyl disulfide (DPS) rescue both these growth defects. Furthermore, the unfolded protein response (UPR) is slightly induced by a DPS treatment. We infer that DPS may change the redox state of important ER-proteins by GSH-oxidation in the ER or, more likely, by directly oxidizing these targets. Therefore, DPS may be useful in genetic studies dealing with unknown factors of the Ero1p-driven pathway. The ero1-1 mutation and the overproduction of Ero1p confer DPS-sensitivity that could be partially related to a more oxidized cytosolic GSH redox potential and the presence of reactive oxidative species (ROS) in the cell.
López-Mirabal
H Reynaldo
HR
Carlsberg Laboratory, Gamle Carlsberg Vej 10, 2500 Copenhagen Valby, Denmark.
Winther
Jakob R
JR
D000693:Anaerobiosis; D004220:Disulfides / Q000378:metabolism*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D020043:Genes, Essential; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D006358:Hot Temperature; D016877:Oxidants; D050862:Oxidoreductases Acting on Sulfur Group Donors; D019704:Protein Disulfide-Isomerases / Q000378:metabolism*; D011725:Pyridines / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
D004220:Disulfides; D005656:Fungal Proteins; D006023:Glycoproteins; D016877:Oxidants; D011725:Pyridines; D029701:Saccharomyces cerevisiae Proteins; C007542:4,4'-dipyridyl disulfide; D050862:Oxidoreductases Acting on Sulfur Group Donors; C113186:ERO1 protein, S cerevisiae; D019704:Protein Disulfide-Isomerases