核毛孔复合体将能量感知与长寿的转录可塑性联系起来
Yifei Zhou1,2, Fasih M Ahsan1,2,3, Alexander A Soukas1,2
1Center for Genomic Medicine and Diabetes Unit, Endocrine Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, United States.
bioRxiv : the preprint server for biology
|March 3, 2025
概括
能量传感器AMPK调节NPP-16/NUP50,通过激活独立于核运输的脂质代谢来延长C. elegans的寿命. 这种保存的信号轴弥合了能量感知和代谢适应.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 衰老研究研究 衰老研究
背景情况:
- 核孔综合体 (NPC) 对于细胞功能至关重要,并且随着年龄的增长而下降.
- 由于NPC的组成,研究个别NPC组件的与年龄相关的作用是复杂的.
- AMP激活蛋白激酶 (AMPK) 是细胞中的主能量传感器.
研究的目的:
- 研究AMPK在调节核素NPP-16/NUP50.0.中的作用.
- 探索NPP-16/NUP50在衰老和新陈代谢中的功能.
- 为了确定AMPK-NPP-16/NUP50轴是否在物种之间保持.
主要方法:
- AMPK.50对NPP-16/NUP50的翻译后调节分析.
- 对脂质代谢基因的转录基因分析.
- 在 *Caenorhabditis elegans * 中进行寿命测定.
- 研究NPP-16/NUP50与转录机器的内在无序区域 (IDR) 相互作用.
主要成果:
- AMPK调节NPP-16/NUP50的丰度,以应对营养的可用性和能量压力.
- 通过促进脂质代谢基因表达,NPP-16/NUP50可以延长*C. elegans*的寿命.
- NPP-16/NUP50的IDR直接与转录机械相互作用,激活催化基因.
- 较高的NPP-16/NUP50水平提高了寿命和对代谢应激的抵抗力.
- 在人类中,AMPK-NPP-16/NUP50信号通路是保留的.
结论:
- 通过AMPK调节NPP-16/NUP50是一种将能量传感与代谢适应联系起来的新机制.
- NPP-16/NUP50具有独立于其正规核运输功能的寿命延长作用.
- 这种保存的信号轴突出了在将细胞能量状态与代谢调节联系起来的古老作用.
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