論文 - 詳細
| RRC ID | 56192 |
|---|---|
| 著者 | 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. |
| タイトル | C. elegans-based screen identifies lysosome-damaging alkaloids that induce STAT3-dependent lysosomal cell death. |
| ジャーナル | 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. |
| 巻・号 | 9(12) |
| ページ | 1013-1026 |
| 公開日 | 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 |
| 引用数 | 7 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 3 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 線虫 | tm1125 tm2388 |