Title |
C. elegans-based screen identifies lysosome-damaging alkaloids that induce STAT3-dependent lysosomal cell death
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Published in |
Protein & Cell, April 2018
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DOI | 10.1007/s13238-018-0520-0 |
Pubmed ID | |
Authors |
Yang Li, Yu Zhang, Qiwen Gan, Meng Xu, Xiao Ding, Guihua Tang, Jingjing Liang, Kai Liu, Xuezhao Liu, Xin Wang, Lingli Guo, Zhiyang Gao, Xiaojiang Hao, Chonglin Yang |
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. |
X Demographics
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Unknown | 3 | 100% |
Demographic breakdown
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Members of the public | 3 | 100% |
Mendeley readers
Geographical breakdown
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Unknown | 21 | 100% |
Demographic breakdown
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Student > Bachelor | 2 | 10% |
Researcher | 2 | 10% |
Student > Ph. D. Student | 2 | 10% |
Lecturer | 1 | 5% |
Other | 1 | 5% |
Other | 3 | 14% |
Unknown | 10 | 48% |
Readers by discipline | Count | As % |
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Biochemistry, Genetics and Molecular Biology | 4 | 19% |
Chemistry | 4 | 19% |
Agricultural and Biological Sciences | 1 | 5% |
Neuroscience | 1 | 5% |
Medicine and Dentistry | 1 | 5% |
Other | 0 | 0% |
Unknown | 10 | 48% |