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ESCRT ‐mediated lysosome repair precedes lysophagy and promotes cell survival
Author(s) -
Radulovic Maja,
Schink Kay O,
Wenzel Eva M,
Nähse Viola,
Bongiovanni Antonino,
Lafont Frank,
Stenmark Harald
Publication year - 2018
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201899753
Subject(s) - reprogramming , library science , medicine , biology , cell , genetics , computer science
Abstract Although lysosomes perform a number of essential cellular functions, damaged lysosomes represent a potential hazard to the cell. Such lysosomes are therefore engulfed by autophagic membranes in the process known as lysophagy, which is initiated by recognition of luminal glycoprotein domains by cytosolic lectins such as Galectin‐3. Here, we show that, under various conditions that cause injury to the lysosome membrane, components of the endosomal sorting complex required for transport ( ESCRT )‐I, ESCRT ‐ II , and ESCRT ‐ III are recruited. This recruitment occurs before that of Galectin‐3 and the lysophagy machinery. Subunits of the ESCRT ‐ III complex show a particularly prominent recruitment, which depends on the ESCRT ‐I component TSG 101 and the TSG 101‐ and ESCRT ‐ III ‐binding protein ALIX . Interference with ESCRT recruitment abolishes lysosome repair and causes otherwise reversible lysosome damage to become cell lethal. Vacuoles containing the intracellular pathogen Coxiella burnetii show reversible ESCRT recruitment, and interference with this recruitment reduces intravacuolar bacterial replication. We conclude that the cell is equipped with an endogenous mechanism for lysosome repair which protects against lysosomal damage‐induced cell death but which also provides a potential advantage for intracellular pathogens.