营养维生素B12通过单碳代谢调节RAS/MAPK介导的细胞命运决策
Ana Cristina Laranjeira1, Simon Berger1,2, Tea Kohlbrenner1
1Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.
Nature communications
|September 17, 2024
概括
饮食维生素B12通过影响单碳代谢和RAS/MAPK通路,影响细胞命运. 这种必不可少的营养素影响了C. elegans的发育和繁殖,对哺乳动物的影响是保留的.
科学领域:
- 细胞生物学 细胞生物学
- 代谢途径 代谢途径
- 发展生物学 发展生物学
背景情况:
- 维生素B12对于单碳代谢至关重要,支持叶酸和氨酸循环.
- RAS/MAPK信号通路调节了关键的细胞命运决定.
- 饮食因素可以影响基本的细胞过程.
研究的目的:
- 为了研究食维生素B12如何影响通过RAS/MAPK通路调解的细胞命运决定.
- 阐明单碳代谢物在维生素B12依赖细胞反应中的作用.
- 为了确定这些效应是否在哺乳动物系统中保持.
主要方法:
- 使用C. elegans作为模型生物来研究食维生素B12的影响.
- 分析了组织特异性反应,包括阴道诱导,生殖细胞亡和卵细胞分化.
- 采用具有激活KRAS和BRAF等位基因的哺乳动物细胞系来评估保存机制.
主要成果:
- 饮食维生素B12显著增加了C. elegans的阴道诱导,生殖细胞亡和卵细胞分化.
- 维生素B12调节胆/脂胆和核酸代谢,影响基因表达和组织素甲基化 (H3K4三甲基化).
- 氨酸对RAS/MAPK调节的表型的影响在哺乳动物细胞中保持.
结论:
- 维生素B12依赖的单碳代谢是RAS/MAPK信号传递的关键调节者.
- 一碳代谢产物作为维生素B12对细胞命运的影响的组织特异调解剂.
- 这些发现强调了维生素B12作为RAS/MAPK信号调节的多种细胞反应的潜在限制因素.
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