饥饿诱导的新陈代谢重新连接会影响mTORC1 in vivo中的组成
Edgar Kaade1, Simone Mausbach1, Nina Erps2
1Institute for Biochemistry and Molecular Biology, Medical Faculty, Rheinische Friedrich-Wilhelms-University of Bonn, 53115, Bonn, Germany.
Scientific reports
|November 16, 2024
概括
饥饿会改变肝脏溶酶体的组成,影响mTORC1信号传递和蛋白质降解途径. 这项研究揭示了特定器官对营养缺乏的反应,突出了禁食期间的适应机制.
科学领域:
- 细胞生物学 细胞生物学
- 代谢过程中的代谢.
- 分子生物学分子生物学
背景情况:
- 溶解体对于细胞适应饥饿至关重要.
- 在饥饿期间对溶解体变化的体内研究有限.
- 了解这些变化对于代谢研究至关重要.
研究的目的:
- 为了研究小鼠在短期 (6小时) 和长期 (24小时) 饥饿期间肝脏溶解体的蛋白质变化.
- 为了检查mTORC1信号传递及其相关复合体在饥饿期间肝脏溶解体中的作用.
- 为了比较饥饿对不同代谢器官 (肝脏,肌肉,大脑) mTORC1活性的影响.
主要方法:
- 来自经过短期和长期饥饿的小鼠肝脏溶解体的蛋白质组分析.
- 测量饥饿标志物 (减肥,体,血糖,3-甲基胺).
- 评估mTORC1信号通路组件 (mTORC1,Ragulator) 和它们在肝脏,肌肉和大脑的溶解体中的活性.
主要成果:
- 短期的饥饿消耗了肝脏的溶酶体mTORC1和Ragulator,减少了mTORC1的酸化.
- 长期的饥饿恢复了肝脏的溶酶体mTORC1活性,但Ragulator仍然减少.
- 肌肉显示mTORC1无活化与长时间的饥饿,而大脑mTORC1活动不受影响.
- 溶酶体中蛋白质体,细胞体,过氧体和线粒体蛋白质的积累表明了自性降解.
结论:
- 在饥饿期间,肝脏 lysosomal 蛋白质组和 mTORC1 信号表现出动态变化.
- 即使在长时间的饥饿期间mTORC1重新激活后,Ragulator复合体的耗尽仍然存在.
- 对mTORC1信号的器官特异性调节有助于在禁食期间的代谢适应.
- 特定蛋白质类型的溶解体积累反映了细胞组件的有序自清除.
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