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 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.

Automated summary

Cell proteostasis includes various processes such as gene transcription, protein folding, and degradation. By analyzing the proteome of T cell-secreted extracellular vesicles (EVs), researchers have found that the chaperonin complex CCT plays a role in the correct folding of specific proteins. When CCT is limited by siRNA, cells undergo changes in lipid composition and metabolic rewiring towards a lipid-dependent metabolism, resulting in increased activity of peroxisomes and mitochondria. This is due to dysregulation of interorganelle contacts between lipid droplets, mitochondria, peroxisomes, and the endolysosomal system. These findings connect proteostasis with lipid metabolism through an unexpected role of CCT.