Related Experiment Video

Updated: Sep 15, 2025

Quantification of Cytosolic vs. Vacuolar Salmonella in Primary Macrophages by Differential Permeabilization
09:25

Quantification of Cytosolic vs. Vacuolar Salmonella in Primary Macrophages by Differential Permeabilization

Published on: July 28, 2015

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Restricting intracellular Salmonella proliferation by coordinating p-TBK1 mediated mitophagy and xenophagy

Jun Li1,2, Yang Yang1, Yao Ge1

  • 1State Key Laboratory of Animal Nutrition, Department of Companion Animal Science, China Agricultural University, Beijing, P. R. China.

Autophagy
|July 15, 2025
PubMed

Insights

Salmonella typhimurium evades host immunity by suppressing mitophagy and xenophagy. The compound fisetin activates mitophagy, restricting bacterial replication and enhancing pathogen clearance.

Area of Science:

  • Cell Biology
  • Immunology
  • Microbiology

Background:

  • Mitophagy is crucial for clearing damaged mitochondria and plays a role in pathogen immune evasion.
  • Salmonella typhimurium (S. typhimurium) is known to interact with host cells, but the precise mechanisms involving mitophagy and xenophagy in its survival remain unclear.

Purpose of the Study:

  • To investigate the role of mitophagy and xenophagy in S. typhimurium infection.
  • To identify potential therapeutic strategies for controlling S. typhimurium by modulating these cellular processes.

Main Methods:

  • In vitro and in vivo experiments using macrophage cell lines and infected mice.
  • Utilized mitophagy inhibitor Mdivi-1 and Pink1 siRNA for mechanistic studies.
  • Performed RNA-Seq transcriptome and metabolomics analyses.
  • Confocal microscopy to visualize mitophagy and xenophagy.

Main Results:

  • S. typhimurium actively represses mitophagy and xenophagy to promote intracellular replication.
  • Fisetin treatment activates mitophagy and subsequently enhances xenophagy, restricting S. typhimurium growth.
  • Fisetin's mechanism involves the recruitment of phosphorylated TBK1 to mitochondria, facilitating Pink1-Parkin mediated mitophagy.
  • Fisetin treatment improved host health parameters in infected mice, an effect reversed by mitophagy inhibition.

Conclusions:

  • S. typhimurium inhibits mitophagy to ensure its survival within host cells.
  • Fisetin acts as a xenophagy enhancer by promoting mitophagy, thereby reducing intracellular Salmonella burden.
  • Targeting mitophagy and xenophagy presents a potential therapeutic avenue against S. typhimurium infections.
Keywords:
Immune escapeSalmonellaTBK1mitophagyxenophagy

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