Rojas-Gómez, AmeliaDosil, Sara GChichón, Francisco JavierFernández-Gallego, NievesFerrarini, AlessiaCalvo, EnriqueCalzada-Fraile, DiegoRequena, SilviaOtón, JoaquinSerrano, AlvaroTarifa, RocioArroyo, MontserratSorrentino, AndreaPereiro, EvaVazquez, JesusValpuesta, José MSánchez-Madrid, FranciscoMartín-Cófreces, Noa B2023-09-052023-09-052023-06J Extracell Vesicles. 2023 Jun;12(6):e12333.http://hdl.handle.net/20.500.12105/16418Cell 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.engVoRhttp://creativecommons.org/licenses/by/4.0/KinesinsExtracellular VesiclesChaperonin Containing TCP-1Lipid MetabolismLipidsAtribución 4.0 Internacional37328936126e1233310.1002/jev2.123332001-3078Journal of extracellular vesiclesopen access