PDF(Pubmed)
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.
摘要：
线粒体自噬对于线粒体质量控制和清除受损线粒体的功能至关重要。这里,我们发现，假伯克霍尔德菌通过III型分泌系统针尖蛋白BipD操纵宿主的线粒体自噬，使其在细胞内存活。我们确认了BipD,通过与BTB蛋白KLHL9和KLHL13结合而与BTB蛋白相互作用。招募NEDD8家族环E3连接酶CUL3以应对假单胞菌感染。虽然显然不参与传染病的监管，KLHL9/KLHL13/CUL3E3连接酶复合物对于小鼠巨噬细胞中线粒体的BipD依赖性泛素化至关重要。机械上,我们通过宿主泛素组谱发现线粒体内膜IMMT作为KLHL9/KLHL13/CUL3复合物的底物。值得注意的是,启动宿主线粒体自噬需要IMMTK211的K63连接的泛素化，从而减少线粒体ROS的产生。这里,我们展示了一种独特的机制，由细菌病原体使用，劫持宿主的线粒体自噬为他们的生存。
