由线粒体应激所导致的转化停滞升级调节了一条 CNOT4-ZNF598 核糖体质量控制通路,该通路对组织稳定具有重要作用
Ji Geng1, Shuangxi Li2,3, Yu Li2,3
1Department of Pathology, Stanford University School of Medicine, Stanford, CA, 94305, USA. jigeng@stanford.edu.
Nature communications
|February 22, 2024
概括
ZNF598蛋白通过感知翻译停滞来调节核糖体质量控制. 它的无处不在可以通过清除缺陷蛋白质来保护线粒体应激和神经退行性疾病.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 神经科学是一个神经科学.
背景情况:
- 翻译控制对于蛋白质组完整性至关重要.
- 核糖体相关质量控制 (RQC) 解决了停滞的翻译问题.
- ZNF598是翻译停滞的关键传感器,但其在多细胞生物中的调节尚不清楚.
研究的目的:
- 为了研究ZNF598.8.的生理调节.
- 阐明ZNF598在线粒体压力和神经退行性疾病中的作用.
主要方法:
- 研究了ZNF598在哺乳动物细胞和Drosophila中的无处不在.
- 在线粒体应激条件下研究ZNF598的功能.
- 利用了神经退行性疾病和患者衍生的细胞的Drosophila模型.
主要成果:
- ZNF598经历了 CNOT4 相关的 K63 相关的无化.
- 在线粒体应激时,ZNF598的水平会增加.
- 在疾病模型中,ZNF598过度表达解决了停滞的翻译,消除了有毒蛋白质,并改善了组织健康.
结论:
- ZNF598通过全方位化进行调节,在线粒体和组织平衡中起着至关重要的作用.
- ZNF598通过解决停滞的翻译和清除异常蛋白质产物来保护神经退行性疾病.
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