| RRC ID |
56192
|
| Author |
Li Y, Zhang Y, Gan Q, Xu M, Ding X, Tang G, Liang J, Liu K, Liu X, Wang X, Guo L, Gao Z, Hao X, Yang C.
|
| Title |
C. elegans-based screen identifies lysosome-damaging alkaloids that induce STAT3-dependent lysosomal cell death.
|
| Journal |
Protein Cell
|
| 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.
|
| Volume |
9(12)
|
| Pages |
1013-1026
|
| Published |
2018-12-1
|
| DOI |
10.1007/s13238-018-0520-0
|
| PII |
10.1007/s13238-018-0520-0
|
| PMID |
29611115
|
| PMC |
PMC6251801
|
| MeSH |
Alkaloids / pharmacology*
Animals
Caenorhabditis elegans / cytology
Caenorhabditis elegans / drug effects*
Caenorhabditis elegans / metabolism
Cell Death / drug effects*
Cell Survival / drug effects
HeLa Cells
Humans
Lysosomes / drug effects*
Lysosomes / pathology
STAT3 Transcription Factor / metabolism*
Signal Transduction / drug effects
|
| IF |
7.575
|
| Times Cited |
7
|
| Resource |
| C.elegans |
tm1125
tm2388 |
