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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Detalles Bibliográficos
Autores: Rojas-Gómez, Amelia, Dosil, Sara G, Chichón, Francisco Javier, Fernández-Gallego, Nieves, Ferrarini, Alessia, Calvo, Enrique, Calzada-Fraile, Diego, Requena, Silvia, Otón, Joaquin, Serrano, Alvaro, Tarifa, Rocio, Arroyo, Montserrat, Sorrentino, Andrea, Pereiro, Eva, Vazquez, Jesus, Valpuesta, José M, Sánchez-Madrid, Francisco, Martín-Cófreces, Noa B
Tipo de recurso: artículo
Fecha de publicación:2023
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/16733
Acceso en línea:http://hdl.handle.net/20.500.12105/16733
Access Level:acceso abierto
Palabra clave:Kinesins
Extracellular Vesicles
Chaperonin Containing TCP-1
Lipid Metabolism
Lipids
Descripción
Sumario: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.