根据线粒体的一碳循环的依赖,PKM2转移了甘油性流量
Mohaned Benzarti1, Laura Neises2, Anais Oudin3
1Cancer Metabolism Group, Department of Cancer Research, Luxembourg Institute of Health, Luxembourg, Luxembourg; Faculty of Science, Technology and Medicine, University of Luxembourg, Belvaux, Luxembourg; Molecular Disease Mechanisms Group, Faculty of Science, Technology and Medicine, Department of Life Sciences and Medicine, University of Luxembourg, Belvaux, Luxembourg.
Cell reports
|February 29, 2024
概括
癌细胞中的糖溶性限制阻断了pyruvate kinase M2 (PKM2) 以促进血清蛋白合成并通过谷氨酸维持TCA循环流动. 线粒体的一碳代谢影响了这种PKM2调节.
科学领域:
- 癌症新陈代谢 癌症新陈代谢
- 细胞的新陈代谢
- 生物化学 生物化学
背景情况:
- 在体外 (in vitro) 建模瘤代谢是复杂的.
- 银河糖用于模拟有限的糖解.
- 已经确立的理论表明,高的糖溶性流量会降低pyruvate kinase异酶M2 (PKM2) 的活性.
研究的目的:
- 为了研究糖溶性限制对PKM2活性的影响.
- 了解细胞是如何适应营养稀缺的.
- 探索谷氨酸和单碳代谢在瘤细胞存活中的作用.
主要方法:
- 利用银河糖作为一个体外工具来诱导糖溶性限制.
- 在营养稀缺条件下分析PKM2活性.
- 研究了谷氨酸在维持TCA循环流量和血清蛋白合成中的作用.
- 研究了删除线粒体一碳 (1C) 循环对PKM2活性的影响.
主要成果:
- 与预期相反,糖溶性限制导致PKM2.2的几乎完全阻断.
- 细胞将碳转移到血清代谢中,尽管资源有限和能量压力有限.
- TCA循环流量和氧气消耗是由谷氨酸维持的.
- 谷氨胺通过PKM2-依赖和独立的途径支持TCA循环流和血清蛋白合成.
- 删除线粒体1C循环会逆转PKM2的阻断,表明交叉通话.
结论:
- 糖溶性限制独特地影响PKM2活动,重定向细胞代谢.
- 谷氨酸在维持新陈代谢平衡和在营养压力下促进增殖方面发挥着至关重要的作用.
- 线粒体1C新陈代谢和细胞质糖解之间的形式依赖交叉调节营养稀缺期间的细胞存活.
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