Plateau P~Lazard M, 2017

Pubmed ID 28303947
Title Exposure to selenomethionine causes selenocysteine misincorporation and protein aggregation in Saccharomyces cerevisiae.
Authors Pierre Plateau, Cosmin Saveanu, Roxane Lestini, Marc Dauplais, Laurence Decourty, Alain Jacquier, Sylvain Blanquet, Myriam Lazard
Abstract Selenomethionine, a dietary supplement with beneficial health effects, becomes toxic if taken in excess. To gain insight into the mechanisms of action of selenomethionine, we screened a collection of ≈5900 Saccharomyces cerevisiae mutants for sensitivity or resistance to growth-limiting amounts of the compound. Genes involved in protein degradation and synthesis were enriched in the obtained datasets, suggesting that selenomethionine causes a proteotoxic stress. We demonstrate that selenomethionine induces an accumulation of protein aggregates by a mechanism that requires de novo protein synthesis. Reduction of translation rates was accompanied by a decrease of protein aggregation and of selenomethionine toxicity. Protein aggregation was supressed in a ∆cys3 mutant unable to synthetize selenocysteine, suggesting that aggregation results from the metabolization of selenomethionine to selenocysteine followed by translational incorporation in the place of cysteine. In support of this mechanism, we were able to detect random substitutions of cysteinyl residues by selenocysteine in a reporter protein. Our results reveal a novel mechanism of toxicity that may have implications in higher eukaryotes.
Citation Sci Rep 2017; 7:44761


Download the list of datasets
Papers Phenotype Conditions Collection Tested mutants Data Details
Plateau P~Lazard M, 2017 growth (relative abundance in pooled culture) selenomethionine [12 uM] hap a 4,342 Quantitative
Plateau P~Lazard M, 2017 growth (relative abundance in pooled culture) selenomethionine [20 uM] hap a 4,299 Quantitative

Curation history

March 21, 2017 Tested strains to load.
March 21, 2017 Data to load.
April 23, 2017 Tested strains loaded.
April 23, 2017 Data loaded.