线粒体新陈代谢的不同模式,T细胞分化和功能
Will Bailis1,2, Justin A Shyer1, Jun Zhao1,3,4
1Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA.
Nature
|June 21, 2019
概括
在T助手1 (TH1) 细胞中,不同的线粒体代谢模式将分离与效应器功能. 综合体I支持增殖和表观遗传变化,而综合体II通过改变新陈代谢来驱动效应器功能.
科学领域:
- 免疫学
- 细胞生物学
- 代谢生物学
背景情况:
- 激活的CD4 T细胞经历了代谢重编程以进行增殖,表观遗传重塑和效应器功能.
- T细胞激活涉及T细胞受体结合,共刺激信号和细胞因子,诱导生物质生成和增殖的糖解程序.
- 虽然信号传导和转录重塑协调T细胞的分化和功能,但细胞生化组成的作用仍然不清楚.
研究的目的:
- 调查不同的线粒体代谢途径是否独立调节T助手1 (TH1) 细胞分化和效应器功能.
- 阐明线粒体新陈代谢影响T细胞增殖,表观遗传修饰和终端功能的生化机制.
主要方法:
- 在小鼠T助手1 (TH1) 细胞中利用了基因操纵,药理干预和代谢学分析的组合.
- 研究了特定的线粒体复合物 (复合物I,复合物II),马酸-酸盐运输和线粒体酸盐出口的作用.
- 对T细胞增殖,基因乙化,基因表达和效应器功能的评估影响.
主要成果:
- 不同的线粒体代谢途径从生化上将TH1细胞与效应器功能分离.
- 通过酸脱酶 (复合II) 进行的三酸循环对于TH1效应体的功能至关重要,但抑制了增殖和基因素乙化.
- 复合物I,酸盐-酸盐穿和线粒体酸盐出口通过维持酸盐合成对T细胞增殖和基因素乙化至关重要.
结论:
- 线粒体代谢在T细胞激活中起着关键的双重作用,不同的途径支持不同的细胞过程.
- 马拉酸-酸盐运输,线粒体酸盐输出和复合I为早期T细胞增殖和表观遗传重塑提供基质.
- 复合II通过消耗这些基质来对抗分化并促进终端效应器功能,突出显示了一种与转录编程并行的生物化学网络,该网络强制执行细胞状态.
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