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Oxidative stress conditions increase the frequency of de novo formation of the yeast [ PSI + ] prion
Author(s) -
Doronina Victoria A.,
Staniforth Gemma L.,
Speldewinde Shaun H.,
Tuite Mick F.,
Grant Chris M.
Publication year - 2015
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.12930
Subject(s) - mutant , yeast , oxidative stress , biology , biochemistry , amyloid (mycology) , sod1 , methionine , superoxide dismutase , oxidative phosphorylation , antioxidant , protein aggregation , glutathione , wild type , microbiology and biotechnology , amino acid , enzyme , gene , botany
Summary 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 S up35 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 S up35 methionine residues in antioxidant mutants and show that overexpression of methionine sulphoxide reductase abrogates both the oxidation of S up35 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 S up35 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.