title: The yeast Tsa1 peroxiredoxin is a ribosome-associated antioxidant.
abstract: 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-molecular-mass forms, whereas a super-chaperone form predominates in high-molecular-mass complexes. Loss of TSA1 results in aggregation of ribosomal proteins, indicating that Tsa1 functions to maintain the integrity of the translation apparatus. In the present study we report 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 cysteine residue is also required for a shift from ribosomes to its high-molecular-mass 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 (reactive oxygen species), 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. In the present study we show that deregulation of Tsa1 in the trr1 mutant specifically promotes translation defects including hypersensitivity to translation inhibitors, increased translational error-rates and ribosomal protein aggregation. These results 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.
authors.affiliation: Faculty of Life Sciences, The University of Manchester, Manchester M13 9PT, UK.
authors.forename: Eleanor W
authors.initials: EW
authors.lastname: Trotter
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Rand
authors.forename: Jill
authors.initials: J
authors.lastname: Vickerstaff
authors.forename: Chris M
authors.initials: CM
authors.lastname: Grant
mesh_terms: D000975:Antioxidants / Q000378:metabolism / Q000502:physiology*; D008954:Models, Biological; D050505:Mutant Proteins / Q000235:genetics / Q000502:physiology; D030781:Organisms, Genetically Modified; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000235:genetics; D009195:Peroxidase / Q000378:metabolism; D010544:Peroxidases / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D054464:Peroxiredoxins / Q000502:physiology*; D011485:Protein Binding; D014176:Protein Biosynthesis / Q000502:physiology; D012270:Ribosomes / Q000378:metabolism* / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000254:growth & development; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D054481:Thioredoxin Reductase 1 / Q000235:genetics; D013879:Thioredoxins / Q000235:genetics
chemical_list: D000975:Antioxidants; D050505:Mutant Proteins; D029701:Saccharomyces cerevisiae Proteins; D013879:Thioredoxins; D010544:Peroxidases; C496253:Tsa1 protein, S cerevisiae; D054464:Peroxiredoxins; D009195:Peroxidase; D054481:Thioredoxin Reductase 1