Exosomes and STUB1/CHIP cooperate to maintain intracellular proteostasis
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Outros Autores: | , , , , , , |
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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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 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
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application/pdf |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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