酸盐的命运通过调节细胞的氧化还原潜力来决定细胞的生长
Ashish G Toshniwal1, Geanette Lam1, Alex J Bott1
1Department of Biochemistry, University of Utah, Salt Lake City, UT 84132, USA.
bioRxiv : the preprint server for biology
|October 10, 2024
概括
改变特种细胞中的酸盐代谢,通过增加NADH/NAD+比率来抑制细胞生长,促进葡萄糖生成而不是糖解. 这种新陈代谢的重新连接抑制了蛋白质合成,阻碍了生物质的生产,尽管激活了生长信号.
科学领域:
- 代谢调节 代谢调节 代谢调节
- 细胞的生长和发展.
- 生物化学 生物化学
背景情况:
- 酸盐是碳水化合物代谢中的关键中间体,平衡能量生产和生物合成.
- 与繁殖细胞相比,它在特殊的转基因后细胞中的作用,比如 *Drosophila* 脂肪体,是不太了解的.
- 在发育过程中, *Drosophila* 脂肪体中的快速细胞生长表明一种独特的代谢调节.
研究的目的:
- 为了研究酸盐代谢在调节细胞生长中的作用,在转移后的细胞中.
- 为了确定操纵酸盐命运是否会影响细胞大小和生物质生产.
- 探索酸盐代谢与促生长信号通路之间的相互作用.
主要方法:
- 研究 *Drosophila* 脂肪体细胞 *in vivo* 和培养的哺乳动物肝细胞 *in vitro*.
- 操纵的线粒体pyruvate进口以改变pyruvate代谢.
- 测量了细胞大小,NADH/NAD+比率,代谢途径活性 (葡萄糖生成,糖解),氨基酸合成和蛋白质合成.
- 评估了促生长信号通路 (mTORC1,Myc,PI3K/Akt) 的激活.
主要成果:
- 增强的线粒体pyruvate进口阻止了细胞生长在两个 * Drosophila * 脂肪体细胞和培养肝细胞.
- 这种抑制与增加的NADH/NAD+比率有关,有利于葡萄糖生成和抑制糖解.
- 氨基酸合成减少导致蛋白质合成减少,从而抑制细胞生长.
- 即使激活了促生长信号通路,细胞生长也被抑制.
结论:
- 酸盐的新陈代谢关键调节细胞大小和生物质的生产在专门的转化后细胞.
- 由增加的NADH/NAD+驱动的对葡萄糖生成的代谢重新连接,取代了促生长信号,以抑制细胞生长.
- 这突显出一种进化保守的机制,控制了能源提取和生物质合成之间的平衡.
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