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Exosomes and STUB1/CHIP cooperate to maintain intracellular proteostasis

2019-10-15Artigo científico Acesso aberto
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dc.contributor.authorFerreira, Joao Vasco
dc.contributor.authorSoares, Ana Rosa
dc.contributor.authorRamalho, José S.
dc.contributor.authorRibeiro-Rodrigues, Teresa
dc.contributor.authorMáximo, Catarina
dc.contributor.authorZuzarte, Mónica
dc.contributor.authorGirão, Henrique
dc.contributor.authorPereira, Paulo
dc.contributor.institutionCentro de Estudos de Doenças Crónicas (CEDOC)
dc.contributor.institutionNOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
dc.contributor.pblPLOS - Public Library of Science
dc.date.accessioned2019-10-28T23:55:52Z
dc.date.available2019-10-28T23:55:52Z
dc.date.issued2019-10-15
dc.description.abstractDeregulation 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.en
dc.description.versionpublishersversion
dc.description.versionpublished
dc.format.extent3100698
dc.identifier.doi10.1371/journal.pone.0223790
dc.identifier.issn1932-6203
dc.identifier.otherPURE: 15223158
dc.identifier.otherPURE UUID: b9e50bcc-80d0-42d3-852a-bde1acd0a476
dc.identifier.otherScopus: 85073463115
dc.identifier.otherPubMed: 31613922
dc.identifier.otherWOS: 000532565700036
dc.identifier.otherORCID: /0000-0002-9908-2290/work/151406793
dc.identifier.urihttp://www.scopus.com/inward/record.url?scp=85073463115&partnerID=8YFLogxK
dc.identifier.urlhttps://www.scopus.com/pages/publications/85073463115
dc.language.isoeng
dc.peerreviewedyes
dc.subjectGeneral Biochemistry,Genetics and Molecular Biology
dc.subjectGeneral Agricultural and Biological Sciences
dc.subjectGeneral
dc.titleExosomes and STUB1/CHIP cooperate to maintain intracellular proteostasisen
dc.typejournal article
degois.publication.issue10
degois.publication.titlePLoS ONE
degois.publication.volume14
dspace.entity.typePublication
rcaap.rightsopenAccess

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