“泛素连接酶”Parkin是“泛素化”和线粒体自吞（受损线粒体的清除中所涉及的自吞类型）所必需的。这项研究显示，Parkin也在先天免疫防御中起作用，用“泛素链”来标记含结核分枝杆菌的吞噬体，并将它们作为异体吞噬（应对细胞内细菌病原体的自吞降解过程）的目标。鉴于线粒体的演化起源被假设是来自一个细菌内共生体，因此Parkin调控用于内源性线粒体（自身）的质量控制和有害细菌病原体（非自身）的清除的同一细胞程序的这个事实是意味深长的。(生物谷 Bioon.com)
生物谷推荐的英文摘要
Nature doi:10.1038/nature12566
The ubiquitin ligase parkin mediates resistance to intracellular pathogens
Paolo S. Manzanillo,1 Janelle S. Ayres,2, 8 Robert O. Watson,1, 8 Angela C. Collins,3 Gianne Souza,1 Chris S. Rae,4 David S. Schneider,5 Ken Nakamura,6, 7 Michael U. Shiloh3 & Jeffery S. Cox1
Ubiquitin-mediated targeting of intracellular bacteria to the autophagy pathway is a key innate defence mechanism against invading microbes, including the important human pathogen Mycobacterium tuberculosis. However, the ubiquitin ligases responsible for catalysing ubiquitin chains that surround intracellular bacteria are poorly understood. The parkin protein is a ubiquitin ligase with a well-established role in mitophagy, and mutations in the parkin gene (PARK2) lead to increased susceptibility to Parkinson’s disease. Surprisingly, genetic polymorphisms in the PARK2 regulatory region are also associated with increased susceptibility to intracellular bacterial pathogens in humans, including Mycobacterium leprae and Salmonella enterica serovar Typhi, but the function of parkin in immunity has remained unexplored. Here we show that parkin has a role in ubiquitin-mediated autophagy of M. tuberculosis. Both parkin-deficient mice and flies are sensitive to various intracellular bacterial infections, indicating parkin has a conserved role in metazoan innate defence. Moreover, our work reveals an unexpected functional link between mitophagy and infectious disease.
