Protein aggregation into insoluble deposits protects from oxidative stress

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 da...

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Authors: Carija, Anita, Navarro, Susanna, Sanchez de Groot, Natalia, Ventura, Salvador
Format: article
Status:Published version
Publication Date:2017
Country:España
Institution:Universitat Pompeu Fabra
Repository:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/35158
Online Access:http://hdl.handle.net/10230/35158
http://dx.doi.org/10.1016/j.redox.2017.03.027
Access Level:Open access
Keyword:Amyloid peptide
Oxidative stress
Protein aggregation
Protein inclusions
Yeast
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oai_identifier_str oai:repositori.upf.edu:10230/35158
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repository_id_str
spelling Protein aggregation into insoluble deposits protects from oxidative stressCarija, AnitaNavarro, SusannaSanchez de Groot, NataliaVentura, SalvadorAmyloid peptideOxidative stressProtein aggregationProtein inclusionsYeastProtein 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.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.Elsevier201820182017info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/35158http://dx.doi.org/10.1016/j.redox.2017.03.027reponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésRedox Biology. 2017 Aug;12:699-711info:eu-repo/grantAgreement/ES/1PE/BFU2013-44763-Pinfo:eu-repo/grantAgreement/ES/1PE/BIO2016-783-78310-R© 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/)http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:repositori.upf.edu:10230/351582026-06-12T07:21:37Z
dc.title.none.fl_str_mv Protein aggregation into insoluble deposits protects from oxidative stress
title Protein aggregation into insoluble deposits protects from oxidative stress
spellingShingle Protein aggregation into insoluble deposits protects from oxidative stress
Carija, Anita
Amyloid peptide
Oxidative stress
Protein aggregation
Protein inclusions
Yeast
title_short Protein aggregation into insoluble deposits protects from oxidative stress
title_full Protein aggregation into insoluble deposits protects from oxidative stress
title_fullStr Protein aggregation into insoluble deposits protects from oxidative stress
title_full_unstemmed Protein aggregation into insoluble deposits protects from oxidative stress
title_sort Protein aggregation into insoluble deposits protects from oxidative stress
dc.creator.none.fl_str_mv Carija, Anita
Navarro, Susanna
Sanchez de Groot, Natalia
Ventura, Salvador
author Carija, Anita
author_facet Carija, Anita
Navarro, Susanna
Sanchez de Groot, Natalia
Ventura, Salvador
author_role author
author2 Navarro, Susanna
Sanchez de Groot, Natalia
Ventura, Salvador
author2_role author
author
author
dc.subject.none.fl_str_mv Amyloid peptide
Oxidative stress
Protein aggregation
Protein inclusions
Yeast
topic Amyloid peptide
Oxidative stress
Protein aggregation
Protein inclusions
Yeast
description 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.
publishDate 2017
dc.date.none.fl_str_mv 2017
2018
2018
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/35158
http://dx.doi.org/10.1016/j.redox.2017.03.027
url http://hdl.handle.net/10230/35158
http://dx.doi.org/10.1016/j.redox.2017.03.027
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Redox Biology. 2017 Aug;12:699-711
info:eu-repo/grantAgreement/ES/1PE/BFU2013-44763-P
info:eu-repo/grantAgreement/ES/1PE/BIO2016-783-78310-R
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Repositorio Digital de la UPF
instname:Universitat Pompeu Fabra
instname_str Universitat Pompeu Fabra
reponame_str Repositorio Digital de la UPF
collection Repositorio Digital de la UPF
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.812455

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