Exosomes and STUB1/CHIP cooperate to maintain intracellular proteostasis

Detalhes bibliográficos
Autor(a) principal: Ferreira, Joao Vasco
Data de Publicação: 2019
Outros Autores: Soares, Ana Rosa, Ramalho, José S., Ribeiro-Rodrigues, Teresa, Máximo, Catarina, Zuzarte, Mónica, Girão, Henrique, Pereira, Paulo
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: https://doi.org/10.1371/journal.pone.0223790
Resumo: Deregulation of proteostasis is a main feature of many age-related diseases, often leading to the accumulation of toxic oligomers and insoluble protein aggregates that accumulate intracellularly or in the extracellular space. To understand the mechanisms whereby toxic or otherwise unwanted proteins are secreted to the extracellular space, we inactivated the quality-control and proteostasis regulator ubiquitin ligase STUB1/CHIP. Data indicated that STUB1 deficiency leads both to the intracellular accumulation of protein aggregates and to an increase in the secretion of small extracellular vesicles (sEVs), including exosomes. Secreted sEVs are enriched in ubiquitinated and/or undegraded proteins and protein oligomers. Data also indicates that oxidative stress induces an increase in the release of sEVs in cells depleted from STUB1. Overall, the results presented here suggest that cells use exosomes to dispose of damaged and/or undegraded proteins as a means to reduce intracellular accumulation of proteotoxic material.
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spelling Exosomes and STUB1/CHIP cooperate to maintain intracellular proteostasisBiochemistry, Genetics and Molecular Biology(all)Agricultural and Biological Sciences(all)GeneralDeregulation of proteostasis is a main feature of many age-related diseases, often leading to the accumulation of toxic oligomers and insoluble protein aggregates that accumulate intracellularly or in the extracellular space. To understand the mechanisms whereby toxic or otherwise unwanted proteins are secreted to the extracellular space, we inactivated the quality-control and proteostasis regulator ubiquitin ligase STUB1/CHIP. Data indicated that STUB1 deficiency leads both to the intracellular accumulation of protein aggregates and to an increase in the secretion of small extracellular vesicles (sEVs), including exosomes. Secreted sEVs are enriched in ubiquitinated and/or undegraded proteins and protein oligomers. Data also indicates that oxidative stress induces an increase in the release of sEVs in cells depleted from STUB1. Overall, the results presented here suggest that cells use exosomes to dispose of damaged and/or undegraded proteins as a means to reduce intracellular accumulation of proteotoxic material.Centro de Estudos de Doenças Crónicas (CEDOC)NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)RUNFerreira, Joao VascoSoares, Ana RosaRamalho, José S.Ribeiro-Rodrigues, TeresaMáximo, CatarinaZuzarte, MónicaGirão, HenriquePereira, Paulo2019-10-28T23:55:52Z2019-10-152019-10-15T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://doi.org/10.1371/journal.pone.0223790eng1932-6203PURE: 15223158http://www.scopus.com/inward/record.url?scp=85073463115&partnerID=8YFLogxKhttps://doi.org/10.1371/journal.pone.0223790info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T04:38:26Zoai:run.unl.pt:10362/85727Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:36:37.689751Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Exosomes and STUB1/CHIP cooperate to maintain intracellular proteostasis
title Exosomes and STUB1/CHIP cooperate to maintain intracellular proteostasis
spellingShingle Exosomes and STUB1/CHIP cooperate to maintain intracellular proteostasis
Ferreira, Joao Vasco
Biochemistry, Genetics and Molecular Biology(all)
Agricultural and Biological Sciences(all)
General
title_short Exosomes and STUB1/CHIP cooperate to maintain intracellular proteostasis
title_full Exosomes and STUB1/CHIP cooperate to maintain intracellular proteostasis
title_fullStr Exosomes and STUB1/CHIP cooperate to maintain intracellular proteostasis
title_full_unstemmed Exosomes and STUB1/CHIP cooperate to maintain intracellular proteostasis
title_sort Exosomes and STUB1/CHIP cooperate to maintain intracellular proteostasis
author Ferreira, Joao Vasco
author_facet Ferreira, Joao Vasco
Soares, Ana Rosa
Ramalho, José S.
Ribeiro-Rodrigues, Teresa
Máximo, Catarina
Zuzarte, Mónica
Girão, Henrique
Pereira, Paulo
author_role author
author2 Soares, Ana Rosa
Ramalho, José S.
Ribeiro-Rodrigues, Teresa
Máximo, Catarina
Zuzarte, Mónica
Girão, Henrique
Pereira, Paulo
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Centro de Estudos de Doenças Crónicas (CEDOC)
NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
RUN
dc.contributor.author.fl_str_mv Ferreira, Joao Vasco
Soares, Ana Rosa
Ramalho, José S.
Ribeiro-Rodrigues, Teresa
Máximo, Catarina
Zuzarte, Mónica
Girão, Henrique
Pereira, Paulo
dc.subject.por.fl_str_mv Biochemistry, Genetics and Molecular Biology(all)
Agricultural and Biological Sciences(all)
General
topic Biochemistry, Genetics and Molecular Biology(all)
Agricultural and Biological Sciences(all)
General
description Deregulation of proteostasis is a main feature of many age-related diseases, often leading to the accumulation of toxic oligomers and insoluble protein aggregates that accumulate intracellularly or in the extracellular space. To understand the mechanisms whereby toxic or otherwise unwanted proteins are secreted to the extracellular space, we inactivated the quality-control and proteostasis regulator ubiquitin ligase STUB1/CHIP. Data indicated that STUB1 deficiency leads both to the intracellular accumulation of protein aggregates and to an increase in the secretion of small extracellular vesicles (sEVs), including exosomes. Secreted sEVs are enriched in ubiquitinated and/or undegraded proteins and protein oligomers. Data also indicates that oxidative stress induces an increase in the release of sEVs in cells depleted from STUB1. Overall, the results presented here suggest that cells use exosomes to dispose of damaged and/or undegraded proteins as a means to reduce intracellular accumulation of proteotoxic material.
publishDate 2019
dc.date.none.fl_str_mv 2019-10-28T23:55:52Z
2019-10-15
2019-10-15T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv https://doi.org/10.1371/journal.pone.0223790
url https://doi.org/10.1371/journal.pone.0223790
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 1932-6203
PURE: 15223158
http://www.scopus.com/inward/record.url?scp=85073463115&partnerID=8YFLogxK
https://doi.org/10.1371/journal.pone.0223790
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reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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