接触抑制诱导静止期间的代谢和转录组重编程是由YAP依赖和YAP独立的机制调解的
Soeun Kang1, Maciek R Antoniewicz2, Nissim Hay3,4
1Department of Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA.
Nature communications
|August 8, 2024
概括
静止细胞重新连接新陈代谢,增加TCA循环流量和呼吸,同时降低糖解. 这种代谢转变通过产生ATP和氨基酸来支持细胞外基质的产生.
科学领域:
- 细胞生物学 细胞生物学
- 代谢工程是代谢工程.
- 生物化学 生物化学
背景情况:
- 代谢重新连接对于细胞周期过渡至关重要,但人们对其了解甚少.
- 接触抑制是细胞静止的一个关键调节器.
研究的目的:
- 研究在扩散到静止过渡期间的代谢变化.
- 阐明支持静止细胞功能的代谢途径.
主要方法:
- 在生殖和静止的小鼠胚胎纤维细胞 (MEF) 中进行C-代谢流量分析.
- 转录组分析以确定基因表达变化.
- 抑制关键的代谢调节者,如线粒体的酸盐载体 (MPC).
主要成果:
- 静止细胞显示降低了葡萄糖分解和增加了TCA循环流和线粒体呼吸.
- 是-关联蛋白 (YAP) 的抑制减少了糖溶性酶表达.
- 诱导的线粒体酸盐载体 (MPC) 表达增加了TCA循环活性.
- 酸盐到酸盐的流量减少,而酸盐脱酶1 (MDH1) 介导的流量反转并升高.
- 基因表达转向细胞外矩阵 (ECM) 生产,抑制YAP依赖和细胞周期基因.
结论:
- 在静止细胞中,高TCA循环流和呼吸对于ATP和氨基酸合成至关重要.
- 代谢重编程支持静止细胞中的新细胞外基因蛋白质合成和分泌.
- 静止细胞易受线粒体中pyruvate载体 (MPC) 抑制的影响.
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