Lysosomal membrane permeabilization or full rupture of lysosomes is a common and severe stress condition that is relevant for degenerative disease, infection and cancer. Cells respond with extensive ubiquitination of damaged lysosomes, which triggers selective macroautophagy/autophagy of the whole organelle, termed lysophagy. We screened an siRNA library targeting human E2-conjugating enzymes and identified UBE2QL1 as critical for efficient lysosome ubiquitination after chemically-induced lysosomal damage. UBE2QL1 translocates to lysosomes upon damage and associates with autophagy regulators. Loss of UBE2QL1-mediated ubiquitination reduces association of the autophagy receptor SQSTM1/p62 and the LC3-decorated phagophore, and prevents recruitment of the ubiquitin-targeted AAA-ATPase VCP/p97 that facilitates lysophagy. Even in unchallenged cells, UBE2QL1 depletion leads to MTOR dissociation and TFEB activation, and mutation of the homolog UBC-25 destabilizes lysosomes in C. elegans, indicating that UBE2QL1 is critical for maintaining lysosome integrity in addition to lysophagy.
SEEK ID: http://localhost:3000/publications/48
PubMed ID: 31679434
Projects: SyNergy - published datasets
Publication type: Journal
Journal: Autophagy
Citation: Autophagy. 2020 Jan;16(1):179-180. doi: 10.1080/15548627.2019.1687217. Epub 2019 Nov 6.
Date Published: 5th Nov 2019
Registered Mode: by PubMed ID
Views: 52
Created: 8th Jul 2024 at 12:35
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