The yeast Tsa1 peroxiredoxin, like other 2-Cys peroxiredoxins, has dual activities as a peroxidase and as a molecular chaperone. Its peroxidase function predominates in lower MW forms, whereas, a super-chaperone form predominates in high MW complexes. Loss of TSA1 results in aggregation of ribosomal proteins indicating that Tsa1 functions to maintain the integrity of the translation apparatus. We report here that Tsa1 functions as an antioxidant on actively translating ribosomes. Its peroxidase activity is required for ribosomal function since mutation of the peroxidatic cysteine residue, which inactivates peroxidase but not chaperone activity, results in sensitivity to translation inhibitors. The peroxidatic Cys residue is also required for a shift from ribosomes to its HMW form in response to peroxide stress. Thus, Tsa1 appears to function predominantly as an antioxidant in protecting both the cytosol and actively translating ribosomes against endogenous ROS, but shifts towards its chaperone function in response to oxidative stress conditions. Analysis of the distribution of Tsa1 in thioredoxin system mutants revealed that the ribosome-associated form of Tsa1 is increased in mutants lacking thioredoxin reductase (trr1) and thioredoxins (trx1 trx2) in parallel with the general increase in total Tsa1 levels which is observed in these mutants. We show that de-regulation of Tsa1 in the trr1 mutant specifically promotes translation defects including hypersensitivity to translation inhibitors, increased translational error-rates and ribosomal protein aggregation. These data have important implications for the role of peroxiredoxins in stress and growth control since peroxiredoxins are likely to be deregulated in a similar manner during many different disease states.
|Evidence ID||Analyze ID||Interactor||Interactor Systematic Name||Interactor||Interactor Systematic Name||Type||Assay||Annotation||Action||Modification||Phenotype||Source||Reference||Note|
|Evidence ID||Analyze ID||Gene||Gene Systematic Name||Gene Ontology Term||Gene Ontology Term ID||Qualifier||Aspect||Method||Evidence||Source||Assigned On||Reference||Annotation Extension|
|Evidence ID||Analyze ID||Gene||Gene Systematic Name||Phenotype||Experiment Type||Experiment Type Category||Mutant Information||Strain Background||Chemical||Details||Reference|
|Evidence ID||Analyze ID||Regulator||Regulator Systematic Name||Target||Target Systematic Name||Experiment||Conditions||Strain||Source||Reference|