mTORC2-NDRG1-CDC42轴对快速到线粒体裂变
Nuria Martinez-Lopez1,2,3,4, Pamela Mattar1,3, Miriam Toledo3,5
1Department of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
Nature cell biology
|June 29, 2023
概括
禁食激活mTORC2,后者酸化NDRG1以促进线粒体裂变并维持呼吸. 这一途径对于营养缺乏期间的细胞适应至关重要.
科学领域:
- 细胞生物学 细胞生物学
- 代谢过程中的代谢.
- 线粒体动力学的动力学
背景情况:
- 禁食会引起生理变化,包括脂肪酸增加和线粒体呼吸,这对生存至关重要.
- 禁食期间控制线粒体适应和呼吸功能的机制尚未完全理解.
研究的目的:
- 阐明mTORC2信号在禁食期间调节线粒体功能的作用.
- 为了确定关键的蛋白质和途径,涉及到禁食诱导的线粒体适应.
主要方法:
- 利用时差成像观察线粒体动态.
- 采用蛋白质组学和小干扰RNA查.
- 进行了表观性实验,以确定通路相互作用.
主要成果:
- 禁食和脂质可用性刺激了哺乳动物目标的拉帕素复合体2 (mTORC2) 活性.
- 激活的mTORC2酸化NDRG1 (NMYC下游调节基因1) 在血清336,维持线粒体裂变.
- 化NDRG1与线粒体相互作用,以DRP1独立的方式促进裂变,并与CDC42 (细胞分裂控制蛋白42) 信号合作.
结论:
- 在禁食期间,通过mTORC2介导的NDRG1酸化对于维持线粒体裂变和呼吸充分性至关重要.
- mTORC2-NDRG1-CDC42轴调节线粒体裂变,这是对营养稀缺的关键适应.
- 意想不到的是,mTORC2在禁食期间重新激活,以驱动线粒体裂变和呼吸,与其在营养过剩期间的合成作用形成对比.
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