The role of ATG5 beyond Atg8ylation and autophagy

This study shows that in the absence of ATG5, but not other core canonical autophagy factors, endolysosomal organelles display a lysosomal hypersensitivity phenotype when subjected to damage. This is in part due to a compromised recruitment of ESCRT proteins to lysosomes in need of repair. Mechanistically, in the absence of ATG5, the ESCRT protein PDCD6IP/ALIX is sequestered by the alternative conjugate ATG12-ATG3, contributing to excessive exocytic processes while not being available for lysosomal repair. Specifically, this condition increases secretion of extracellular vesicles and particles, and leads to excessive degranulation in neutrophils. Our findings uncover unique functions of ATG5 outside of the autophagy and Atg8ylation paradigm. This finding is of in vivo relevance for tuberculosis pathogenesis as modeled in mice.PMID:37876292 | DOI:10.1080/15548627.2023.2273703

Source: Autophagy - October 25, 2023 Category: Cytology Authors: Fulong Wang Einar S Trosdal Masroor Ahmad Paddar Thabata L A Duque Lee Allers Michal Mudd Prithvi R Akepati Ruheena Javed Jingyue Jia Michelle Salemi Brett Phinney Vojo Deretic Source Type: research