C. elegans-based screen identifies lysosome-damaging alkaloids that induce STAT3-dependent lysosomal cell death
Protein & Cell
;
(12): 1013-1026, 2018.
Article
in English
| WPRIM
| ID: wpr-757971
ABSTRACT
Lysosomes are degradation and signaling centers within the cell, and their dysfunction impairs a wide variety of cellular processes. To understand the cellular effect of lysosome damage, we screened natural small-molecule compounds that induce lysosomal abnormality using Caenorhabditis elegans (C. elegans) as a model system. A group of vobasinyl-ibogan type bisindole alkaloids (ervachinines A-D) were identified that caused lysosome enlargement in C. elegans macrophage-like cells. Intriguingly, these compounds triggered cell death in the germ line independently of the canonical apoptosis pathway. In mammalian cells, ervachinines A-D induced lysosomal enlargement and damage, leading to leakage of cathepsin proteases, inhibition of autophagosome degradation and necrotic cell death. Further analysis revealed that this ervachinine-induced lysosome damage and lysosomal cell death depended on STAT3 signaling, but not RIP1 or RIP3 signaling. These findings suggest that lysosome-damaging compounds are promising reagents for dissecting signaling mechanisms underlying lysosome homeostasis and lysosome-related human disorders.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Pathology
/
Pharmacology
/
HeLa Cells
/
Signal Transduction
/
Cell Survival
/
Cell Death
/
Caenorhabditis elegans
/
Cell Biology
/
Alkaloids
/
STAT3 Transcription Factor
Type of study:
Prognostic study
Limits:
Animals
/
Humans
Language:
English
Journal:
Protein & Cell
Year:
2018
Type:
Article
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