抗菌因子APOL3结合了线粒体DNA排泄和I型IFN诱导的溶酶体损伤
Dominic A Ritacco1, Hamna Shahnawaz1, Antonia Oduguwa1
1Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY.
bioRxiv : the preprint server for biology
|June 6, 2025
概括
溶酶体损伤触发了线粒体DNA的释放和I型干扰素的产生. 抗菌蛋白APOL3选择性地透了内线粒体膜,增强了对感染的天生的免疫反应.
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:
- 溶解体损伤作为内源性危险信号,但其在先天免疫和特定信号通路中的作用尚未完全理解.
- 线粒体DNA (mtDNA) 释放是细胞应激反应的关键事件,但控制其排放的机制是复杂的.
研究的目的:
- 阐明连接 lysosomal 损伤与线粒体 DNA 流失和 I 型干扰素生产的途径.
- 识别 lysosomal 损伤向线粒体发出信号并影响天生的免疫力的分子机制.
主要方法:
- 使用了细胞和生化复合试验.
- 研究了阿波利波蛋白L-3 (APOL3) 对溶酶体损伤和II型干扰素 (IFN-γ) 起因反应的作用.
- 使用显微镜和生物化学分析检查了线粒体外膜和内膜透性 (MOMP和IMM透性).
- 评估了cGAS/STING信号激活的情况.
主要成果:
- 溶酶体损伤通过BAK/BAX.诱导线粒体外膜透 (MOMP) 通过BAK/BAX.
- 第二种类型的IFN (IFN-γ) 激发细胞表达APOL3,一种抗菌蛋白.
- APOL3可选择性地透经历MOMP的线粒体的内部线粒体膜 (IMM),增强mtDNA释放.
- APOL3通过溶解心脂蛋白来透IMM,从而激活cGAS/STING信号传输.
- 这一途径将溶酶体损伤与I型干扰素的产生联系起来.
结论:
- 一个免疫诱导的途径将溶酶体损伤与mtDNA流量和I型干扰素生产联系起来.
- 抗菌蛋白APOL3通过透IMM,在促进mtDNA释放方面发挥着至关重要的作用.
- 这种机制突显了细胞如何利用抗菌效应剂来增强受伤和感染期间的先天免疫反应.
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