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Oxidative stress conditions increase the frequency ofde novoformation of the yeast [PSI+] prion

Doronina, Victoria A., Staniforth, Gemma L., Speldewinde, Shaun H., Tuite, Mick F., Grant, Chris M. (2015) Oxidative stress conditions increase the frequency ofde novoformation of the yeast [PSI+] prion. Molecular Microbiology, 96 (1). pp. 163-174. ISSN 0950-382X. (doi:10.1111/mmi.12930) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided) (KAR id:47821)

The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided. (Contact us about this Publication)
Official URL
http://dx.doi.org/10.1111/mmi.12930

Abstract

Prions are self-perpetuating amyloid protein aggregates which underlie various neurodegenerative diseases in mammals and heritable traits in yeast. The molecular basis of how yeast and mammalian prions form spontaneously into infectious amyloid-like structures is poorly understood. We have explored the hypothesis that oxidative stress is a general trigger for prion formation using the yeast [PSI+] prion, which is the altered conformation of the Sup35 translation termination factor. We show that the frequency of [PSI+] prion formation is elevated under conditions of oxidative stress and in mutants lacking key antioxidants. We detect increased oxidation of Sup35 methionine residues in antioxidant mutants and show that overexpression of methionine sulphoxide reductase abrogates both the oxidation of Sup35 and its conversion to the [PSI+] prion. [PSI+] prion formation is particularly elevated in a mutant lacking the Sod1 Cu,Zn-superoxide dismutase. We have used fluorescence microscopy to show that the de novo appearance of [PSI+] is both rapid and increased in frequency in this mutant. Finally, electron microscopy analysis of native Sup35 reveals that similar fibrillar structures are formed in both the wild-type and antioxidant mutants. Together, our data indicate that oxidative stress is a general trigger of [PSI+] formation, which can be alleviated by antioxidant defenses.

Item Type: Article
DOI/Identification number: 10.1111/mmi.12930
Subjects: Q Science
Divisions: Faculties > Sciences > School of Biosciences
Depositing User: Sue Davies
Date Deposited: 01 Apr 2015 09:22 UTC
Last Modified: 06 May 2020 03:12 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/47821 (The current URI for this page, for reference purposes)
Tuite, Mick F.: https://orcid.org/0000-0002-5214-540X
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