效应器
GPX4
生物
结核分枝杆菌
蛋白质精氨酸甲基转移酶5
组蛋白
病菌
致病岛
细胞生物学
甲基转移酶
微生物学
肺结核
毒力
遗传学
甲基化
氧化应激
生物化学
谷胱甘肽过氧化物酶
基因
超氧化物歧化酶
医学
病理
作者
Lihua Qiang,Yong Zhang,Zehui Lei,Zhe Lü,Shasha Tan,Pupu Ge,Qiyao Chai,Mengyuan Zhao,Xinwen Zhang,Bingxi Li,Yu Pang,Lingqiang Zhang,Cui Hua Liu,Jing Wang
标识
DOI:10.1038/s41467-023-37148-x
摘要
Abstract Ferroptosis is a lipid peroxidation-driven and iron-dependent programmed cell death involved in multiple physical processes and various diseases. Emerging evidence suggests that several pathogens manipulate ferroptosis for their pathogenicity and dissemination, but the underlying molecular mechanisms remain elusive. Here, we identify that protein tyrosine phosphatase A (PtpA), an effector secreted by tuberculosis (TB)-causing pathogen Mycobacterium tuberculosis (Mtb), triggers ferroptosis to promote Mtb pathogenicity and dissemination. Mechanistically, PtpA, through its Cys11 site, interacts with host RanGDP to enter host cell nucleus. Then, the nuclear PtpA enhances asymmetric dimethylation of histone H3 arginine 2 (H3R2me2a) via targeting protein arginine methyltransferase 6 (PRMT6), thus inhibiting glutathione peroxidase 4 (GPX4) expression, eventually inducing ferroptosis to promote Mtb pathogenicity and dissemination. Taken together, our findings provide insights into molecular mechanisms of pathogen-induced ferroptosis, indicating a potential TB treatment via blocking Mtb PtpA-host PRMT6 interface to target GPX4-dependent ferroptosis.
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