QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Vol. 17, Issue 1, 387-401, January 2006

This Article Full Text Full Text (PDF) All Versions of this Article: E05-06-0520v1 17/1/387    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rand, J. D. Articles by Grant, C. M. Search for Related Content PubMed PubMed Citation Articles by Rand, J. D. Articles by Grant, C. M.

The Thioredoxin System Protects Ribosomes against Stress-induced Aggregation

The University of Manchester, Faculty of Life Sciences, Manchester M13 9PT, United Kingdom

Submitted June 10, 2005; Revised October 12, 2005; Accepted October 17, 2005
Monitoring Editor: Jeffrey Brodsky

We previously showed that thioredoxins are required for dithiothreitol (DTT) tolerance, suggesting they maintain redox homeostasis in response to both oxidative and reductive stress conditions. In this present study, we screened the complete set of viable deletion strains in Saccharomyces cerevisiae for sensitivity to DTT to identify cell functions involved in resistance to reductive stress. We identified 195 mutants, whose gene products are localized throughout the cell. DTT-sensitive mutants were distributed among most major biological processes, but they particularly affected gene expression, metabolism, and the secretory pathway. Strikingly, a mutant lacking TSA1, encoding a peroxiredoxin, showed a similar sensitivity to DTT as a thioredoxin mutant. Epistasis analysis indicated that thioredoxins function upstream of Tsa1 in providing tolerance to DTT. Our data show that the chaperone function of Tsa1, rather than its peroxidase function, is required for this activity. Cells lacking TSA1 were found to accumulate aggregated proteins, and this was exacerbated by exposure to DTT. Analysis of the protein aggregates revealed that they are predominantly composed of ribosomal proteins. Furthermore, aggregation was found to correlate with an inhibition of translation initiation. We propose that Tsa1 normally functions to chaperone misassembled ribosomal proteins, preventing the toxicity that arises from their aggregation.

Address correspondence to: Chris M. Grant (chris.grant{at}manchester.ac.uk).

This article has been cited by other articles:

				R. Bhabhra, D. L. Richie, H. S. Kim, W. C. Nierman, J. Fortwendel, J. P. Aris, J. C. Rhodes, and D. S. Askew Impaired Ribosome Biogenesis Disrupts the Integration between Morphogenesis and Nuclear Duplication during the Germination of Aspergillus fumigatus Eukaryot. Cell, April 1, 2008; 7(4): 575 - 583. [Abstract] [Full Text] [PDF]

				T. L. Clanton Hypoxia-induced reactive oxygen species formation in skeletal muscle J Appl Physiol, June 1, 2007; 102(6): 2379 - 2388. [Abstract] [Full Text] [PDF]

				G. Monteiro, B. B. Horta, D. C. Pimenta, O. Augusto, and L. E. S. Netto Reduction of 1-Cys peroxiredoxins by ascorbate changes the thiol-specific antioxidant paradigm, revealing another function of vitamin C PNAS, March 20, 2007; 104(12): 4886 - 4891. [Abstract] [Full Text] [PDF]

				C.-Y. Wu, A. J. Bird, D. R. Winge, and D. J. Eide Regulation of the Yeast TSA1 Peroxiredoxin by ZAP1 Is an Adaptive Response to the Oxidative Stress of Zinc Deficiency J. Biol. Chem., January 26, 2007; 282(4): 2184 - 2195. [Abstract] [Full Text] [PDF]

				E. W. Trotter, E. J. Collinson, I. W. Dawes, and C. M. Grant Old Yellow Enzymes Protect against Acrolein Toxicity in the Yeast Saccharomyces cerevisiae. Appl. Envir. Microbiol., July 1, 2006; 72(7): 4885 - 4892. [Abstract] [Full Text] [PDF]