The destination of a damaged lysosome is either being repaired if the damage is small or degraded through a lysosome-specific macroautophagy/autophagy pathway named lysophagy when the damage is too extensive to repair. Even though previous studies report lumenal glycan exposure during lysosome damage as a signal to trigger lysophagy, it is possibly beneficial for cells to initiate lysophagy earlier than membrane rupture. In a recently published article, Gahlot et al. determined that SPART/SPG20 senses lipid-packing defects and recruits and activates the ubiquitin ligase ITCH, which labels damaged lysosomes with ubiquitin chains to initiate lysophagy.
Keywords: ESCRT; lipid-packing defect; lysophagy; lysosome damage; ubiquitination.