Exosomes and STUB1/CHIP cooperate to maintain intracellular proteostasis

Autoři: Joao Vasco Ferreira aff001;  Ana Rosa Soares aff001;  José S. Ramalho aff001;  Teresa Ribeiro-Rodrigues aff002;  Catarina Máximo aff001;  Mónica Zuzarte aff002;  Henrique Girão aff002;  Paulo Pereira aff001
Působiště autorů: CEDOC, Chronic Diseases Research Centre, NOVA Medical School|Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Campo dos Mártires da Pátria, Lisboa, Portugal aff001;  Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, Azinhaga de Santa Comba, Coimbra, Portugal aff002
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
doi: 10.1371/journal.pone.0223790


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.

Klíčová slova:

Goats – Membrane proteins – Oligomers – Oxidative stress – Protein secretion – Secretion – Vesicles – Exosomes


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2019 Číslo 10