内质网
生物
细胞生物学
细胞凋亡
未折叠蛋白反应
生物化学
作者
Qiao Pan,Yujuan Zhang,Tong Liu,Qingyuan Xu,Wenbao Qi,Jiuqing Xin
出处
期刊:PLOS Pathogens
[Public Library of Science]
日期:2024-05-24
卷期号:20 (5): e1012266-e1012266
标识
DOI:10.1371/journal.ppat.1012266
摘要
Mycoplasmas are minimal but notorious bacteria that infect humans and animals. These genome-reduced organisms have evolved strategies to overcome host apoptotic defense and establish persistent infection. Here, using Mycoplasma bovis as a model, we demonstrate that mycoplasma glycine cleavage system (GCS) H protein (GcvH) targets the endoplasmic reticulum (ER) to hijack host apoptosis facilitating bacterial infection. Mechanically, GcvH interacts with the ER-resident kinase Brsk2 and stabilizes it by blocking its autophagic degradation. Brsk2 subsequently disturbs unfolded protein response (UPR) signaling, thereby inhibiting the key apoptotic molecule CHOP expression and ER-mediated intrinsic apoptotic pathway. CHOP mediates a cross-talk between ER- and mitochondria-mediated intrinsic apoptosis. The GcvH N-terminal amino acid 31–35 region is necessary for GcvH interaction with Brsk2, as well as for GcvH to exert anti-apoptotic and potentially pro-infective functions. Notably, targeting Brsk2 to dampen apoptosis may be a conserved strategy for GCS-containing mycoplasmas. Our study reveals a novel role for the conserved metabolic route protein GcvH in Mycoplasma species. It also sheds light on how genome-reduced bacteria exploit a limited number of genomic proteins to resist host cell apoptosis thereby facilitating pathogenesis.
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