Chaperonin CCT controls extracellular vesicle production and cell metabolism through kinesin dynamics

Cell proteostasis includes gene transcription, protein translation, folding of de novo proteins, post-translational modifications, secretion, degradation and recycling. By profiling the proteome of extracellular vesicles (EVs) from T cells, we have found the chaperonin complex CCT, involved in the c...

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Detalhes bibliográficos
Autores: Rojas-Gómez, Amelia, Dosil, S. G., Chichón, Francisco Javier, Fernández-Gallego, Nieves, Ferrarini, Alessia, Calvo, Enrique, Calzada-Fraile, Diego, Requena, Silvia, Otón, Joaquín, Serrano, Álvaro, Tarifa, Rocío, Arroyo, Montserrat, Sorrentino, A., Pereiro, Eva, Vázquez, Jesús, Valpuesta, José M., Sánchez-Madrid, Francisco, Martín-Cófreces, Noa Beatriz
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/362902
Acesso em linha:http://hdl.handle.net/10261/362902
https://api.elsevier.com/content/abstract/scopus_id/85162082519
Access Level:acceso abierto
Palavra-chave:CCT
chaperonin
extracellular vesicle
lipid droplet
lipidomic
peroxisome
Descrição
Resumo:Cell proteostasis includes gene transcription, protein translation, folding of de novo proteins, post-translational modifications, secretion, degradation and recycling. By profiling the proteome of extracellular vesicles (EVs) from T cells, we have found the chaperonin complex CCT, involved in the correct folding of particular proteins. By limiting CCT cell-content by siRNA, cells undergo altered lipid composition and metabolic rewiring towards a lipid-dependent metabolism, with increased activity of peroxisomes and mitochondria. This is due to dysregulation of the dynamics of interorganelle contacts between lipid droplets, mitochondria, peroxisomes and the endolysosomal system. This process accelerates the biogenesis of multivesicular bodies leading to higher EV production through the dynamic regulation of microtubule-based kinesin motors. These findings connect proteostasis with lipid metabolism through an unexpected role of CCT.