C. elegans-based screen identifies lysosome-damaging alkaloids that induce STAT3-dependent lysosomal cell death

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	C. elegans-based screen identifies lysosome-damaging alkaloids that induce STAT3-dependent lysosomal cell death
	Li, Yang; Zhang, Yu; Gan, Qiwen; Xu, Meng; Ding, Xiao; Tang, Guihua; Liang, Jingjing; Liu, Kai; Liu, Xuezhao; Wang, Xin; Guo, Lingli; Gao, Zhiyang; Hao, Xiaojiang; Yang, Chonglin
	2018
Source Publication	PROTEIN & CELL
ISSN	1674-800X
Volume	9 Issue:12 Pages: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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