Chaperonin CCT controls extracellular vesicle production and cell metabolism through kinesin dynamics
Abstract 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...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-06-01
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| Series: | Journal of Extracellular Vesicles |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/jev2.12333 |
| _version_ | 1797797953088258048 |
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| author | Amelia Rojas‐Gómez Sara G. Dosil Francisco J. Chichón Nieves Fernández‐Gallego Alessia Ferrarini Enrique Calvo Diego Calzada‐Fraile Silvia Requena Joaquin Otón Alvaro Serrano Rocio Tarifa Montserrat Arroyo Andrea Sorrentino Eva Pereiro Jesus Vázquez José M. Valpuesta Francisco Sánchez‐Madrid Noa B. Martín‐Cófreces |
| author_facet | Amelia Rojas‐Gómez Sara G. Dosil Francisco J. Chichón Nieves Fernández‐Gallego Alessia Ferrarini Enrique Calvo Diego Calzada‐Fraile Silvia Requena Joaquin Otón Alvaro Serrano Rocio Tarifa Montserrat Arroyo Andrea Sorrentino Eva Pereiro Jesus Vázquez José M. Valpuesta Francisco Sánchez‐Madrid Noa B. Martín‐Cófreces |
| author_sort | Amelia Rojas‐Gómez |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-13T03:56:05Z |
| format | Article |
| id | doaj.art-92e772c6f8d44bdbb9870fce780f13ea |
| institution | Directory Open Access Journal |
| issn | 2001-3078 |
| language | English |
| last_indexed | 2024-03-13T03:56:05Z |
| publishDate | 2023-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Extracellular Vesicles |
| spelling | doaj.art-92e772c6f8d44bdbb9870fce780f13ea2023-06-22T05:06:00ZengWileyJournal of Extracellular Vesicles2001-30782023-06-01126n/an/a10.1002/jev2.12333Chaperonin CCT controls extracellular vesicle production and cell metabolism through kinesin dynamicsAmelia Rojas‐Gómez0Sara G. Dosil1Francisco J. Chichón2Nieves Fernández‐Gallego3Alessia Ferrarini4Enrique Calvo5Diego Calzada‐Fraile6Silvia Requena7Joaquin Otón8Alvaro Serrano9Rocio Tarifa10Montserrat Arroyo11Andrea Sorrentino12Eva Pereiro13Jesus Vázquez14José M. Valpuesta15Francisco Sánchez‐Madrid16Noa B. Martín‐Cófreces17Immunology Service Hospital Universitario de la Princesa, UAM, IIS‐IP Madrid SpainImmunology Service Hospital Universitario de la Princesa, UAM, IIS‐IP Madrid SpainCryoelectron Microscopy Unit Centro Nacional de Biotecnología (CNB‐CSIC) Madrid SpainImmunology Service Hospital Universitario de la Princesa, UAM, IIS‐IP Madrid SpainLaboratory of Cardiovascular Proteomics Fundación Centro Nacional de Investigaciones Cardiovasculares‐Carlos III Madrid SpainLaboratory of Cardiovascular Proteomics Fundación Centro Nacional de Investigaciones Cardiovasculares‐Carlos III Madrid SpainArea of Vascular Pathophysiology, Laboratory of Intercellular Communication Fundación Centro Nacional de Investigaciones Cardiovasculares‐Carlos III Madrid SpainImmunology Service Hospital Universitario de la Princesa, UAM, IIS‐IP Madrid SpainStructural Studies Division MRC Laboratory of Molecular Biology Cambridge UKArea of Vascular Pathophysiology, Laboratory of Intercellular Communication Fundación Centro Nacional de Investigaciones Cardiovasculares‐Carlos III Madrid SpainLaboratory of Cardiovascular Proteomics Fundación Centro Nacional de Investigaciones Cardiovasculares‐Carlos III Madrid SpainImmunology Service Hospital Universitario de la Princesa, UAM, IIS‐IP Madrid SpainALBA Synchrotron Light Source Barcelona SpainALBA Synchrotron Light Source Barcelona SpainLaboratory of Cardiovascular Proteomics Fundación Centro Nacional de Investigaciones Cardiovasculares‐Carlos III Madrid SpainDepartment of Macromolecular Structure Centro Nacional de Biotecnología (CNB‐CSIC) Madrid SpainImmunology Service Hospital Universitario de la Princesa, UAM, IIS‐IP Madrid SpainImmunology Service Hospital Universitario de la Princesa, UAM, IIS‐IP Madrid SpainAbstract 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.https://doi.org/10.1002/jev2.12333CCTchaperoninextracellular vesiclelipid dropletlipidomicperoxisome |
| spellingShingle | Amelia Rojas‐Gómez Sara G. Dosil Francisco J. Chichón Nieves Fernández‐Gallego Alessia Ferrarini Enrique Calvo Diego Calzada‐Fraile Silvia Requena Joaquin Otón Alvaro Serrano Rocio Tarifa Montserrat Arroyo Andrea Sorrentino Eva Pereiro Jesus Vázquez José M. Valpuesta Francisco Sánchez‐Madrid Noa B. Martín‐Cófreces Chaperonin CCT controls extracellular vesicle production and cell metabolism through kinesin dynamics Journal of Extracellular Vesicles CCT chaperonin extracellular vesicle lipid droplet lipidomic peroxisome |
| title | Chaperonin CCT controls extracellular vesicle production and cell metabolism through kinesin dynamics |
| title_full | Chaperonin CCT controls extracellular vesicle production and cell metabolism through kinesin dynamics |
| title_fullStr | Chaperonin CCT controls extracellular vesicle production and cell metabolism through kinesin dynamics |
| title_full_unstemmed | Chaperonin CCT controls extracellular vesicle production and cell metabolism through kinesin dynamics |
| title_short | Chaperonin CCT controls extracellular vesicle production and cell metabolism through kinesin dynamics |
| title_sort | chaperonin cct controls extracellular vesicle production and cell metabolism through kinesin dynamics |
| topic | CCT chaperonin extracellular vesicle lipid droplet lipidomic peroxisome |
| url | https://doi.org/10.1002/jev2.12333 |
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