细胞染色体c氧化酶依赖的呼吸对于T细胞激活,增殖和记忆形成至关重要
Tatiana N Tarasenko1, Emily Warren1, Bharati Singh1
1Metabolism, Infection, and Immunity Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
Nature communications
|December 4, 2025
概括
线粒体呼吸 (MR) 对于T细胞的激活和功能至关重要,即使没有质子. 通过替代氧化酶 (AOX) 恢复电子流,挽救了T细胞的增殖和免疫力.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞的新陈代谢
- 线粒体生物学 线粒体生物学
背景情况:
- 激活T细胞需要代谢转变,常常强调有氧糖解.
- 线粒体呼吸 (MR) 在T细胞功能中的确切作用仍然不完全理解.
研究的目的:
- 调查MR对T细胞激活和功能的必要性和充分性,独立于质子.
- 阐明不同线粒体复合体对T细胞代谢支持的贡献.
主要方法:
- 设计了缺乏COX的T细胞来表达非质子替代氧化酶 (AOX).
- 评估T细胞的增殖,分化 (效应和记忆) 和抗病毒免疫力.
- 分析了电子流量,膜潜力,ATP生产和代谢途径贡献.
主要成果:
- 在缺乏COX的T细胞中,AOX表达恢复了电子流,膜潜力和ATP生产.
- 恢复的MR挽救了T细胞的增殖,效应/记忆的分化和抗病毒免疫力.
- 综合体I为依赖MR的T细胞功能提供了必要的电子输入,而综合体II和DHODH提供了适度的支持.
结论:
- 线粒体呼吸 (MR) 对于T细胞的激活和功能是必要的和充分的,不论质子转位.
- 保持上游电子输入对于MR介导的T细胞代谢支持至关重要.
- 即使在恢复的MR中,高血糖分解仍然存在,这表明复杂的氧化还原信号相互作用.
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