Evidence for the Presence of a Second Electron Donor for the Cytoplasmic Thioredoxins in the Yeast Saccharomyces cerevisiae

In yeast, the cytoplasmic thioredoxin system is composed of NADPH, thioredoxin reductase-1 (TRR1) and 2 thioredoxingenes (TRX1, TRX2). In this study, using yeast knockout mutants for TRR1, TRX1 and TRX2 genes, the role of the thioredoxin system in methionine sulfoxide reduction was investigated. Cells lacking both TRX1 and TRX2 genes simultaneously were not ableto reduce methionine sulfoxides to methionine; however, mutants missing the TRR1 gene were able to reduce methionine sulfoxidesto methionine, which showed that electrons could be transferred from NADPH to thioredoxins in the absence of TRR1. Similar results were observed for 3-phosphoadenosine 5-phosphosulfate reduction in the inorganic sulfate assimilation pathway. Results from both assays suggested that yeast cells have additional cytoplasmic thioredoxin reductase activity that could compensate formethionine sulfoxide reduction and sulfate assimilation in the absence of TRR1. This report also constitutes the first evidence that thioredoxins are the in vivo electron donors for methionine sulfoxide reductases in yeast.