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Mitochondrial injury induced by a Salmonella genotoxin triggers the proinflammatory senescence-associated secretory phenotype

GSE247045 Homo sapiens Expression profiling by high throughput sequencing 9 samples Submitted 2024/03/30 Platform GPL24676
Summary
Bacterial genotoxins can damage host cells by targeting their chromosomal DNA. Salmonella Typhi the causative pathogen of typhoid fever in humans, secretes an essential genotoxin called typhoid toxin, which can induce cellular senescence. Here we show that typhoid toxin triggers the senescence-associated secretory phenotype (SASP) by disrupting mitochondrial function, including a decrease in mitochondrial DNA (mtDNA) content and a disturbance of redox homeostasis within mitochondria. This disruption causes the release of mtDNA into the cytosol, which activates type I interferon via the cGAS-STING pathway. We also demonstrate that the GCN2-mediated integrated stress response modulates the upregulation of inflammatory components depending on the STING signaling axis. These SASP factors can propagate the senescence effect to CD4 T cells, potentially leading to senescence in these cells. Our research provides a novel insight into how bacterial genotoxins target mitochondria to induce a proinflammatory SASP, which could be a promising therapeutic target for an anti-toxin intervention.
Published in
Mitochondrial injury induced by a Salmonella genotoxin triggers the proinflammatory senescence-associated secretory phenotype
Chen HY, Hsieh WC, Liu YC et al. · Nature communications 2024 · PMID 38555361 · doi:10.1038/s41467-024-47190-y
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Also filed as BioProject PRJNA1036122 and SRA study SRP470321. Searching any of these in the dataset finder brings you back here.

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