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.

中文翻译：

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泛素结合酶UBE2QL1对溶酶体完整性和噬菌体的调节。

溶酶体膜透化或溶酶体完全破裂是一种常见的严重应激状况，与变性疾病，感染和癌症有关。细胞对受损的溶酶体进行广泛的泛素化反应，从而触发整个细胞器的选择性巨噬自噬/自噬，称为溶菌吞噬。我们筛选了针对人E2结合酶的siRNA文库，并确定UBE2QL1对化学诱导的溶酶体破坏后有效的溶酶体泛素化至关重要。UBE2QL1在受损时易位至溶酶体，并与自噬调节剂结合。UBE2QL1介导的泛素化作用的丧失减少了自噬受体SQSTM1 / p62和LC3修饰的吞噬细胞的结合，并阻止了泛素靶向的AAA-ATPase VCP / p97的募集，从而促进了溶菌吞噬。即使在没有挑战的牢房中，