促炎细胞因子
表型
衰老
沙门氏菌
生物
细胞生物学
线粒体
DNA损伤
背景(考古学)
遗传学
基因
炎症
免疫学
DNA
细菌
古生物学
作者
Han‐Yi Chen,Wan-Chen Hsieh,Y Liu,Huei-Ying Li,P. Liu,Yu-Ting Hsu,Shao-Chun Hsu,An-Chi Luo,Wei‐Ting Kuo,Yi-Jhen Huang,Gunn‐Guang Liou,Michael Lin,Chun-Jung Ko,Hsing-Chen Tsai,Shu-Han Chang
标识
DOI:10.1038/s41467-024-47190-y
摘要
Abstract Bacterial genotoxins damage host cells by targeting their chromosomal DNA. In the present study, we demonstrate that a genotoxin of Salmonella Typhi, typhoid toxin, triggers the senescence-associated secretory phenotype (SASP) by damaging mitochondrial DNA. The actions of typhoid toxin disrupt mitochondrial DNA integrity, leading to mitochondrial dysfunction and disturbance of redox homeostasis. Consequently, it facilitates the release of damaged mitochondrial DNA into the cytosol, activating type I interferon via the cGAS-STING pathway. We also reveal that the GCN2-mediated integrated stress response plays a role in the upregulation of inflammatory components depending on the STING signaling axis. These SASP factors can propagate the senescence effect on T cells, leading to senescence in these cells. These findings provide insights into how a bacterial genotoxin targets mitochondria to trigger a proinflammatory SASP, highlighting a potential therapeutic target for an anti-toxin intervention.
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