粒体自噬
泛素连接酶
细胞生物学
类鼻疽伯克霍尔德菌
生物
线粒体
泛素
细胞内寄生虫
伯克氏菌属
自噬
微生物学
细胞内
遗传学
细菌
细胞凋亡
基因
作者
Dongqi Nan,Chenglong Rao,Zhiheng Tang,Wenbo Yang,Pan Wu,Jiangao Chen,Yupei Xia,Jingmin Yan,Wenzheng Liu,Ziyuan Zhang,Xuhu Mao,Hai Chen,Yaling Liao,Mao Xuhu,Xiaoyun Liu,Quanming Zou,Qian Li
标识
DOI:10.1038/s41467-024-48824-x
摘要
Abstract Mitophagy is critical for mitochondrial quality control and function to clear damaged mitochondria. Here, we found that Burkholderia pseudomallei maneuvered host mitophagy for its intracellular survival through the type III secretion system needle tip protein BipD. We identified BipD, interacting with BTB-containing proteins KLHL9 and KLHL13 by binding to the Back and Kelch domains, recruited NEDD8 family RING E3 ligase CUL3 in response to B. pseudomallei infection. Although evidently not involved in regulation of infectious diseases, KLHL9/KLHL13/CUL3 E3 ligase complex was essential for BipD-dependent ubiquitination of mitochondria in mouse macrophages. Mechanistically, we discovered the inner mitochondrial membrane IMMT via host ubiquitome profiling as a substrate of KLHL9/KLHL13/CUL3 complex. Notably, K63-linked ubiquitination of IMMT K211 was required for initiating host mitophagy, thereby reducing mitochondrial ROS production. Here, we show a unique mechanism used by bacterial pathogens that hijacks host mitophagy for their survival.
科研通智能强力驱动
Strongly Powered by AbleSci AI