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: | http://hdl.handle.net/10316/107237 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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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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7160 |
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Exosomes and STUB1/CHIP cooperate to maintain intracellular proteostasisDeregulation 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.Public Library of Science2019info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/107237http://hdl.handle.net/10316/107237https://doi.org/10.1371/journal.pone.0223790eng1932-6203316139221932-6203Ferreira, João VascoSoares, Ana RosaRamalho, José S.Ribeiro-Rodrigues, TeresaMáximo, CatarinaZuzarte, MónicaGirão, HenriquePereira, Pauloinfo: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:RCAAP2023-06-15T11:28:12Zoai:estudogeral.uc.pt:10316/107237Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:23:37.547230Repositório 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, João Vasco |
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, João Vasco |
author_facet |
Ferreira, João 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.author.fl_str_mv |
Ferreira, João Vasco Soares, Ana Rosa Ramalho, José S. Ribeiro-Rodrigues, Teresa Máximo, Catarina Zuzarte, Mónica Girão, Henrique Pereira, Paulo |
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 |
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 |
http://hdl.handle.net/10316/107237 http://hdl.handle.net/10316/107237 https://doi.org/10.1371/journal.pone.0223790 |
url |
http://hdl.handle.net/10316/107237 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 31613922 1932-6203 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Public Library of Science |
publisher.none.fl_str_mv |
Public Library of Science |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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1799134122989322240 |