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

Han-Yi Chen, Wan-Chen Hsieh, Yu-Chieh Liu, Huei-Ying Li, Po-Yo Liu, Yu-Ting Hsu, Shao-Chun Hsu, An-Chi Luo, Wei-Chen Kuo, Yi-Jhen Huang, Gan-Guang Liou, Meng-Yun Lin, Chun-Jung Ko, Hsing-Chen Tsai and Shu-Jung Chang ()
Additional contact information
Han-Yi Chen: National Taiwan University
Wan-Chen Hsieh: National Tsing Hua University
Yu-Chieh Liu: National Taiwan University
Huei-Ying Li: National Taiwan University
Po-Yo Liu: National Taiwan University
Yu-Ting Hsu: National Taiwan University
Shao-Chun Hsu: National Taiwan University
An-Chi Luo: National Taiwan University
Wei-Chen Kuo: National Taiwan University
Yi-Jhen Huang: National Taiwan University
Gan-Guang Liou: National Taiwan University
Meng-Yun Lin: National Taiwan University
Chun-Jung Ko: National Taiwan University
Hsing-Chen Tsai: National Taiwan University
Shu-Jung Chang: National Taiwan University

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: 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.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-47190-y Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47190-y

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-47190-y

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().