Page 224 - ebook

[B. Cell Biology/Stem Cell] B-47

Isolation of lysosomal activator regulating lysosomal

damages and cell death

Heemin Park¹, Shin-Hyeon Ryu¹, Seo-Hyun Kim¹, Yong-Keun Jung¹*

¹School of Biological Science, Seoul National University, Seoul 08826, Korea

Lysosomes contribute to maintaining cellular homeostasis via degradation and recycling of subcellular substances
called autophagy, along with a protective action against foreign materials, such as pathogens, and cellular protein

aggregates. Therefore, cells avoid cytotoxicity of the invading pathogen or suppress cell death by degrading
cytotoxic proteins and its aggregates through the lysosomal function. We aimed to isolate small molecules that

affect lysosomal damages and activities. In this study, we established a cell-based lysosomal activity assay and
screened a bioactive compound library to isolate new mediators affecting lysosomal damage. We generated

HeLa/GFP-Galectin3 stable cell line and observed GFP-Gal3 puncta formation when exposed to lysosomotropic
LLOME. We isolated several compounds that affected the LLOME-induced GFP-Gal3 puncta formation. Among them,

we found that mA receptor antagonist (mARA) rescued the processing of cathepsin D and the lysosomal activity as
assayed with DQ-red BSA. In addition, we found that mARA alleviated LLOME-induced apoptosis. Thus, we intend

to broaden our understanding on the lysosomal regulation to lysosomal disease models.