Exposure to selenomethionine causes selenocysteine misincorporation and protein aggregation in Saccharomyces cerevisiae. - Institut Pasteur Accéder directement au contenu
Article Dans Une Revue Scientific Reports Année : 2017

Exposure to selenomethionine causes selenocysteine misincorporation and protein aggregation in Saccharomyces cerevisiae.

Résumé

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.
Fichier principal
Vignette du fichier
2017_Plateau_et_al_Scientific_Reports.pdf (2.8 Mo) Télécharger le fichier
Origine : Publication financée par une institution
Loading...

Dates et versions

pasteur-01496769 , version 1 (27-03-2017)

Licence

Paternité

Identifiants

Citer

Pierre Plateau, Cosmin Saveanu, Roxane Lestini, Marc Dauplais, Laurence Decourty, et al.. Exposure to selenomethionine causes selenocysteine misincorporation and protein aggregation in Saccharomyces cerevisiae.. Scientific Reports, 2017, 7, pp.44761. ⟨10.1038/srep44761⟩. ⟨pasteur-01496769⟩
550 Consultations
228 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More