2. Academic Validation
  3. Autophagy is involved in Salmonella Typhimurium-induced ferroptosis in macrophages

Autophagy is involved in Salmonella Typhimurium-induced ferroptosis in macrophages

  • Vet Microbiol. 2025 Jun:305:110538. doi: 10.1016/j.vetmic.2025.110538.
Wei Liu 1,  Daobin Fu 2,  Chuanyuan Di 2,  Jing Sun 3,  Penggang Liu 2
Affiliations

Affiliations

  • 1 College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu Province 225009, PR China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou, Jiangsu Province 225009, China. Electronic address: liuw@yzu.edu.cn.
  • 2 College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu Province 225009, PR China.
  • 3 College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu Province 225009, PR China; Institute of Comparative Medicine, Yangzhou University, Yangzhou, Jiangsu Province 225009, PR China.
PMID: 40311251 DOI: 10.1016/j.vetmic.2025.110538
Abstract

Salmonella is one of the most common zoonotic pathogens, posing a significant threat to both animal and human health. Our previous study demonstrated that Autophagy plays a crucial role in restricting the intracellular growth of Salmonella. This study aims to investigate the effect of Autophagy in Salmonella Typhimurium (S. Typhimurium)-induced Ferroptosis. First, we found that S. Typhimurium induced lipid peroxidation by increasing intracellular Fe2 + levels, promoting lipid oxidation, and inhibiting the antioxidant pathway. S. Typhimurium-induced lipid peroxidation led to Ferroptosis in macrophages. Further results revealed that S. Typhimurium triggered ferritin degradation by NCOA4-mediated ferritinophagy. Additionally, S. Typhimurium-induced chaperone-mediated Autophagy (CMA) degraded GPX4 through TAK1-HSC70 signaling pathway. Notably, GPX4 is involved in intracellular S. Typhimurium release. Overall, Autophagy was essential for S. Typhimurium induced-ferroptosis, TAK1 not only facilitated Autophagy to eliminate intracellular bacteria but also promoted Bacterial release.

Keywords

Autophagy; Ferroptosis; Macrophages; Salmonella Typhimurium.

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