A phosphoinositide signalling pathway mediates rapid lysosomal repair.

ABSTRACT: Lysosomal dysfunction has been increasingly linked to disease and normal ageing^1,2. Lysosomal membrane permeabilization (LMP), a hallmark of lysosome-related diseases, can be triggered by diverse cellular stressors³. Given the damaging contents of lysosomes, LMP must be rapidly resolved, although the underlying mechanisms are poorly understood. Here, using an unbiased proteomic approach, we show that LMP stimulates a phosphoinositide-initiated membrane tethering and lipid transport (PITT) pathway for rapid lysosomal repair. Upon LMP, phosphatidylinositol-4 kinase type 2α (PI4K2A) accumulates rapidly on damaged lysosomes, generating high levels of the lipid messenger phosphatidylinositol-4-phosphate. Lysosomal phosphatidylinositol-4-phosphate in turn recruits multiple

SUBMITTER: Tan JX 

PROVIDER: S-EPMC9450835 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature