Lysosomes serve as both degradation and recycling centers and signaling hubs to maintain cell and tissue homeostasis. Lysosome dysfunction causes a wide variety of human disorders such as lysosomal storage diseases (LSDs), neurodegenerative diseases and cancer. We establish C. elegans as a multicellular model to dissect lysosome homeostasis (biogenesis, activity, dynamics, membrane integrity, and reformation) at an organismal level and investigate lysosome-dependent cell degradation processes.
As acidic organelles containing ~60 acid hydrolases, the 7-10 nm limiting membrane of lysosomes preserves the integrity of lysosomes and protects cellular constituents from unwanted degradation. The integrity of lysosomes is vital for cell homeostasis and viability, but the mechanisms by which lysosomal membrane stability is maintained are not well understood. We expressed the endomembrane damage reporter Galectin-3 (GFP::Gal3) and performed genetic screens to search for lysosome integrity defective (lid) mutants. From the screens, we isolated lid mutations that affect lysosomal membrane proteins and lipid metabolism pathways. In this talk, I will present our recent work on the characterization of the lid genes in the maintenance of lysosome membrane integrity and function.