The ubiquitin-conjugating enzyme UBE2QL1 coordinates lysophagy in response to endolysosomal damage

ABSTRACT: The autophagic clearance of damaged lysosomes by lysophagy involves extensive modification of the organelle with ubiquitin, but the underlying ubiquitination machinery is still poorly characterized. Here, we use an siRNA screening approach and identify human UBE2QL1 as a major regulator of lysosomal ubiquitination, lysophagy and cell survival after lysosomal damage. UBE2QL1 translocates to permeabilized lysosomes where it associates with damage sensors, ubiquitination targets and lysophagy effectors. UBE2QL1 knockdown reduces ubiquitination and accumulation of the critical autophagy receptor p62, and abrogates recruitment of the AAA-ATPase VCP/p97, which is essential for efficient lysophagy. Crucially, it affects association of LC3B with damaged lysosomes indicating that autophagosome form

SUBMITTER: Prof. Hemmo Meyer 

PROVIDER: S-SCDT-EMBOR-2019-48014-T | biostudies-other |

REPOSITORIES: biostudies-other