ZFAND6促进了TRAF2依赖的线粒,以抑制cGAS-STING信号传输
Kashif Shaikh1, Melissa Bowman2, Sarah M McCormick2
1Department of Microbiology and Immunology, Penn State College of Medicine, Hershey, PA 17033, USA.
iScience
|January 15, 2025
概括
ZFAND6蛋白质通过促进线粒体,清除受损的线粒体来维持线粒体健康. 缺少它会增加ROS,并触发免疫反应,增强病毒抵抗力.
科学领域:
- 细胞生物学 细胞生物学
- 免疫学 免疫学 免疫学
- 线粒体生物学 线粒体生物学
背景情况:
- ZFAND6 (Zinc Finger And NUMB Like 6) 是一种参与瘤亡因子 (TNF) 信号传递的蛋白质.
- 它与TNF受体相关因子2 (TRAF2) 和多比基链相互作用.
研究的目的:
- 研究ZFAND6在维护线粒体平衡中之前未被描述的功能.
- 阐明ZFAND6调节甲基的机制及其对细胞反应的影响.
主要方法:
- 在骨髓衍生巨细胞 (BMDMs) 中删除ZFAND6.
- 评估活性氧物种 (ROS) 水平和线粒体积累.
- 分析线粒体DNA (mtDNA) 释放和干扰素刺激基因表达.
- 研究干扰素基因 (STING) 途径刺激者的作用.
- 检查ZFAND6与TRAF2和cIAP1.1的相互作用.
主要成果:
- 在BMDM中ZFAND6的删除导致ROS增加和线粒体受损,原因是线粒体的受损.
- 线粒体DNA释放到细胞质中触发了STING-依赖的ISG表达.
- 这导致对病毒感染的抗性增强.
- 发现ZFAND6可以弥合TRAF2-cIAP1的相互作用,并将TRAF2招募到受损的线粒体中,从而启动线粒细胞灭菌.
结论:
- 在维护线粒体平衡中,ZFAND6通过促进线粒体吸食起着至关重要的作用.
- 该蛋白质通过一个依赖于TRAF2-cIAP1的机制促进受损线粒体的清除.
- 通过ZFAND6介导的线粒会影响先天免疫反应和病毒抗性.
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