The mitochondrial protein ERAL1 suppresses RNA virus infection by facilitating RIG-I-like receptor signaling
The mitochondrial protein ERAL1 suppresses RNA virus infection by facilitating RIG-I-like receptor signaling
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DOI：
10.1016/j.celrep.2020.108631
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发表时间：
2021-01-19
期刊：
影响因子：
8.8
通讯作者：
You, Fuping
中科院分区：
文献类型：
--
作者：
Li, Siji;Kuang, Ming;You, Fuping
线粒体不仅作为先天免疫信号转导的平台，还通过将线粒体 DNA 和 RNA 释放到细胞质中来增强免疫反应。然而，线粒体基质蛋白是否可以被释放并参与免疫反应仍然是个谜。在这里，我们通过使用基于邻近的标记技术将线粒体蛋白 ERA G 蛋白样 1 (ERAL1) 鉴定为线粒体抗病毒信号蛋白 (MAVS) 相互作用蛋白。 ERAL1 缺陷显着降低了 RNA 病毒触发的下游抗病毒信号。此外，与野生型小鼠相比，ERAL1缺陷型小鼠在RNA病毒感染后更容易死亡。病毒感染后，ERAL1通过BAX/BAK孔从线粒体释放。胞质 ERAL1 促进赖氨酸 63 (K63) 连接的视黄酸诱导基因 1 (RIG-I)/黑色素瘤分化相关基因 5 (MDA5) 泛素化，并促进下游 MAVS 聚合，从而正向调节抗病毒反应。
Mitochondria not only serve as a platform for innate immune signaling transduction but also enhance immune responses by releasing mitochondrial DNA and RNA into the cytoplasm. However, whether mitochondrial matrix proteins could be liberated and involved in immune responses remains enigmatic. Here, we identify the mitochondrial protein ERA G-protein-like 1 (ERAL1) as a mitochondrial antiviral signaling protein (MAVS)-interacting protein by using proximity-based labeling technology. ERAL1 deficiency markedly reduces the downstream antiviral signaling triggered by RNA viruses. Moreover, ERAL1-deficient mice are more susceptible to lethality following RNA virus infection than wild-type mice. After virus infection, ERAL1 is released from mitochondria through the BAX/BAK pore. The cytosolic ERAL1 facilitates lysine 63 (K63)-linked ubiquitination of retinoicacid inducible gene-1 (RIG-I)/melanoma differentiation-associated gene 5 (MDA5) and promotes downstream MAVS polymerization, thus positively regulating antiviral responses.