Fiche du document
14 février 2022
- handle: 10670/1.o2e795
- doi: 10.1038/s41419-022-04591-5
Ce document est mis à disposition selon les termes de la Licence Creative Commons Paternité 4.0 International. / This work is licensed under a Creative Commons Attribution 4.0 International License. , https://creativecommons.org/licenses/by/4.0/
Mots-clés
Apoptotic exosome‐like vesicles Apoptosis Autophagy Autolysosome Endothelial 56 cells Exosome Perlecan Serum starvationSujets proches
Germ theory Life (Biology)--Origin Plasmogeny Origin of life Abiogenesis Heterogenesis Life, Origin of Biogenesis PlasmogonyCiter ce document
Déborah Beillevaire et al., « Autolysosomes and caspase-3 control the biogenesis and release of immunogenic apoptotic exosomes », Papyrus : le dépôt institutionnel de l'Université de Montréal, ID : 10.1038/s41419-022-04591-5
Métriques
Partage / Export
Résumé
Apoptotic exosome-like vesicles (ApoExos) are a novel type of extracellular vesicle that contribute to the propagation of inflammation at sites of vascular injury when released by dying cells. ApoExos are characterized by the presence of the C-terminal perlecan LG3 fragment and 20S proteasome, and they are produced downstream of caspase-3 activation. In the present study, we assessed the relative roles of autophagy and caspase-3-mediated pathways in controlling the biogenesis and secretion of immunogenic ApoExos. Using electron microscopy and confocal immunofluorescence microscopy in serum-starved endothelial cells, we identified large autolysosomes resulting from the fusion of lysosomes, multivesicular bodies, and autophagosomes as a site of ApoExo biogenesis. Inhibition of autophagy with ATG7 siRNA or biochemical inhibitors (wortmannin and bafilomycin) coupled with proteomics analysis showed that autophagy regulated the processing of perlecan into LG3 and its loading onto ApoExos but was dispensable for ApoExo biogenesis. Caspase-3 activation was identified using caspase-3-deficient endothelial cells or caspase inhibitors as a pivotal regulator of fusion events between autolysosomes and the cell membrane, therefore regulating the release of immunogenic ApoExos. Collectively, these findings identified autolysosomes as a site of ApoExo biogenesis and caspase-3 as a crucial regulator of autolysosome cell membrane interactions involved in the secretion of immunogenic ApoExos.