Abstract / Summary
Mastitis, driven predominantly by Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae and Streptococcus species, remains a leading cause of economic loss and antimicrobial use in dairy production. Growing evidence implicates ferroptosis—an iron-dependent, non-apoptotic cell death executed through uncontrolled membrane lipid peroxidation—as a central mechanism of mammary epithelial injury during intramammary infection. Synthesizing evidence from bovine, caprine and murine systems, this review shows that phylogenetically diverse mastitis pathogens converge on a shared three-pillar ferroptotic program: autophagic liberation of catalytic iron via ferritinophagy, mitophagy and chaperone-mediated degradation of glutathione peroxidase 4 (GPX4); lipid-metabolic remodeling that expands peroxidation-susceptible phospholipid substrates; and collapse of the system Xc−/glutathione (GSH)/GPX4 antioxidant axis under Nrf2 control. Viral, xenobiotic, nanomaterial and microbiota-driven insults all engage the same program. The endpoint is convergent, not pathogen-specific. Anti-ferroptotic interventions vary in mechanism, from phytochemicals and selenium nanomaterials to extracellular vesicles and engineered stem cells. Most act on the same few regulatory nodes, chiefly Nrf2, SIRT1, SLC7A11 and GPX4. Ferroptosis-associated genes are being tested as biomarkers for resistance breeding. We grade studies by how directly ferroptosis was shown, separating direct evidence from inference based on upstream omics alone. Questions remain about cell-type-specific roles, timing during natural infection, and whether models translate to the field.