Exposure to selenomethionine causes selenocysteine misincorporation and protein aggregation in Saccharomyces cerevisiae
| Autor: | Plateau, Pierre, Saveanu, Cosmin, Lestini, Roxane, Dauplais, Marc, Decourty, Laurence, Jacquier, Alain, Blanquet, Sylvain, Lazard, Myriam |
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| Přispěvatelé: | Laboratoire de Biochimie de l'Ecole polytechnique (BIOC), École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS), Génétique des Interactions macromoléculaires, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Optique et Biosciences (LOB), École polytechnique (X)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Saveanu, Cosmin, Génétique des Interactions macromoléculaires / Genetics of Macromolecular Interactions, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Saccharomyces cerevisiae Proteins
Reproducibility of Results [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry Molecular Biology/Molecular biology Saccharomyces cerevisiae [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry Molecular Biology/Molecular biology Article Selenocysteine Protein Aggregates Gene Ontology Databases as Topic [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry Molecular Biology/Genomics [q-bio.GN] [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry Molecular Biology/Genomics [q-bio.GN] Amino Acid Sequence [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry Molecular Biology/Biochemistry [q-bio.BM] Peptides Selenomethionine [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry Molecular Biology/Biochemistry [q-bio.BM] Gene Deletion |
| Zdroj: | Scientific Reports Scientific Reports, Nature Publishing Group, 2017, 7, pp.44761. ⟨10.1038/srep44761⟩ Scientific Reports, 2017, 7, pp.44761. ⟨10.1038/srep44761⟩ |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep44761 |
| Popis: | International audience; 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. |
| Databáze: | OpenAIRE |
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