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C. elegans-based screen identifies lysosome-damaging alkaloids that induce STAT3-dependent lysosomal cell death | |
Li, Yang; Zhang, Yu![]() ![]() ![]() ![]() | |
2018 | |
Source Publication | PROTEIN & CELL
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ISSN | 1674-800X |
Volume | 9Issue:12Pages:1013-1026 |
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. |
Indexed By | SCI |
Language | 英语 |
Document Type | 期刊论文 |
Identifier | http://ir.kib.ac.cn/handle/151853/64675 |
Collection | 中国科学院昆明植物研究所 |
Recommended Citation GB/T 7714 | Li, Yang,Zhang, Yu,Gan, Qiwen,et al. C. elegans-based screen identifies lysosome-damaging alkaloids that induce STAT3-dependent lysosomal cell death[J]. PROTEIN & CELL,2018,9(12):1013-1026. |
APA | Li, Yang.,Zhang, Yu.,Gan, Qiwen.,Xu, Meng.,Ding, Xiao.,...&Yang, Chonglin.(2018).C. elegans-based screen identifies lysosome-damaging alkaloids that induce STAT3-dependent lysosomal cell death.PROTEIN & CELL,9(12),1013-1026. |
MLA | Li, Yang,et al."C. elegans-based screen identifies lysosome-damaging alkaloids that induce STAT3-dependent lysosomal cell death".PROTEIN & CELL 9.12(2018):1013-1026. |
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