The ubiquitin ligase parkin mediates resistance to intracellular pathogens.
The ubiquitin ligase parkin mediates resistance to intracellular pathogens.
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作者：
泛素介导的细胞内细菌靶向自噬途径是对抗入侵微生物的关键先天防御机制，包括重要的人类病原体结核分枝杆菌。然而，泛素连接酶负责催化细胞内细菌周围的泛素链知之甚少。PARKIN是一种泛素连接酶，在线粒体自噬中具有明确的作用，PARKIN基因（Park2）突变导致帕金森病易感性增加。令人惊讶的是，Park2调控区的遗传多态性也与人类对胞内细菌病原体（包括麻风分枝杆菌和伤寒沙门氏菌）的易感性增加有关，但PARKIN在免疫中的功能尚未探索。在这里，我们表明PARKIN在泛素介导的M.结核PARKIN缺陷小鼠和果蝇对各种细胞内细菌感染都很敏感，这表明PARKIN在后生动物的先天防御中起着保守的作用。此外，我们的工作揭示了线粒体自噬和传染病之间意想不到的功能联系。
Ubiquitin-mediated targeting of intracellular bacteria to the autophagy pathway is a key innate defense mechanism against invading microbes, including the important human pathogen Mycobacterium tuberculosis. However, the ubiquitin ligases responsible for catalyzing ubiquitin chains that surround intracellular bacteria are poorly understood. PARKIN 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 typhi, but the function of PARKIN in immunity remains unexplored. Here we show that PARKIN plays a role in ubiquitin-mediated autophagy of M. tuberculosis. Both PARKIN-deficient mice and flies are sensitive to various intracellular bacterial infections, suggesting PARKIN plays a conserved role in metazoan innate defense. Moreover, our work reveals an unexpected functional link between mitophagy and infectious disease.
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影响因子：
6.7
作者：
Collins CA;De Mazière A;van Dijk S;Carlsson F;Klumperman J;Brown EJ
通讯作者：
Brown EJ
LRR和环域蛋白LRSAM1是一种E3连接酶，对于细胞内沙门氏菌的泛素依赖性自噬至关重要。
影响因子：
30.3
作者：
Huett A;Heath RJ;Begun J;Sassi SO;Baxt LA;Vyas JM;Goldberg MB;Xavier RJ
通讯作者：
Xavier RJ
影响因子：
64.8
作者：
Mira, MT;Alcaïs, A;Schurr, E
通讯作者：
Schurr, E
影响因子：
4.8
作者：
Goldberg, MS;Fleming, SM;Shen, J
通讯作者：
Shen, J
影响因子：
3.4
作者：
Houben, Diane;Demangel, Caroline;Peters, Peter J.
通讯作者：
Peters, Peter J.