核毛孔复合体将能量感知与长寿的转录性可塑性联系起来
Yifei Zhou1, Fasih M Ahsan2, Sinclair W Emans2
1Center for Genomic Medicine and Diabetes Unit, Endocrine Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Molecular cell
|September 24, 2025
概括
AMP激活蛋白激酶 (AMPK) 调节核蛋白NPP-16/NUP50,通过激活脂质代谢基因,独立促进寿命和代谢防御. 这种保存的信号轴将能量传感与适应联系起来.
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的复杂性,研究个别NPC组件的与年龄相关的作用是很困难的.
研究的目的:
- 研究AMP激活蛋白激酶 (AMPK) 在调节核蛋白NPP-16/NUP50中的作用.
- 探索NPP-16/NUP50在衰老和代谢过程中的功能.
主要方法:
- 在不同的营养和能量条件下,研究了AMPK对NPP-16/NUP50的翻译后调节.
- 评估了NPP-16/NUP50对脂质代谢基因的转录激活的影响.
- 检查了NPP-16/NUP50的内在无序区域 (IDR) 在基因交换激活中的作用.
- 研究了高NPP-16/NUP50水平对*Caenorhabditis elegans*的寿命和抗压力的影响.
- 证实了人类细胞中AMPK-NUP50信号通路的保存.
主要成果:
- 根据营养的可用性和能量状态,AMPK调节NPP-16/NUP50的丰度.
- NPP-16/NUP50通过促进脂肪代谢基因转录,独立于其核运输功能,延长了*C. elegans*的寿命.
- NPP-16/NUP50的IDR直接与转录机制相互作用,以激活代谢基因促进体.
- 增加NPP-16/NUP50水平可以提高寿命和代谢应激防御能力.
- AMPK-NUP50信号通路是从*C. elegans*到人类的进化过程中保持的.
结论:
- AMPK-NPP-16/NUP50信号通路代表了一种新的机制,将细胞能量传感与代谢适应和寿命联系起来.
- NPP-16/NUP50在触媒基因的交换激活中的作用为其在核运输之外的功能提供了新的视角.
- 这条保存的路径突出了古代在将能量恒温与寿命调节之间的桥梁中发挥的基本作用.
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