Protein aggregation into insoluble deposits protects from oxidative stress

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• dc.contributor.author Carija, Anitaca
• dc.contributor.author Navarro, Susannaca
• dc.contributor.author Sanchez de Groot, Nataliaca
• dc.contributor.author Ventura, Salvadorca
• dc.date.accessioned 2018-07-16T08:16:50Z
• dc.date.available 2018-07-16T08:16:50Z
• dc.date.issued 2017
• dc.description.abstract Protein misfolding and aggregation have been associated with the onset of neurodegenerative disorders. Recent studies demonstrate that the aggregation process can result in a high diversity of protein conformational states, however the identity of the specific species responsible for the cellular damage is still unclear. Here, we use yeast as a model to systematically analyse the intracellular effect of expressing 21 variants of the amyloid-ß-peptide, engineered to cover a continuous range of intrinsic aggregation propensities. We demonstrate the existence of a striking negative correlation between the aggregation propensity of a given variant and the oxidative stress it elicits. Interestingly, each variant generates a specific distribution of protein assemblies in the cell. This allowed us to identify the aggregated species that remain diffusely distributed in the cytosol and are unable to coalesce into large protein inclusions as those causing the highest levels of oxidative damage. Overall, our results indicate that the formation of large insoluble aggregates may act as a protective mechanism to avoid cellular oxidative stress.
• dc.description.sponsorship We thank Cristina Visentin for help with H2O2 and catalase measurements. This work was funded by the Spanish Ministry of Economy and Competitiveness (BFU2013-44763-P and BIO2016-783-78310-R to S.V.). S.V. has been granted an ICREA ACADEMIA award.
• dc.format.mimetype application/pdf
• dc.identifier.citation Carija A, Navarro S, de Groot NS, Ventura S. Protein aggregation into insoluble deposits protects from oxidative stress. Redox Biol. 2017 Aug;12:699-711. DOI: 10.1016/j.redox.2017.03.027
• dc.identifier.doi http://dx.doi.org/10.1016/j.redox.2017.03.027
• dc.identifier.issn 2213-2317
• dc.identifier.uri http://hdl.handle.net/10230/35158
• dc.language.iso eng
• dc.publisher Elsevierca
• dc.relation.ispartof Redox Biology. 2017 Aug;12:699-711
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2013-44763-P
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BIO2016-783-78310-R
• dc.rights © 2017 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
• dc.subject.keyword Amyloid peptide
• dc.subject.keyword Oxidative stress
• dc.subject.keyword Protein aggregation
• dc.subject.keyword Protein inclusions
• dc.subject.keyword Yeast
• dc.title Protein aggregation into insoluble deposits protects from oxidative stressca
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion