Role of Ferroptosis in the Redox Biology of Mycotoxins

Ferroptosis, an iron-dependent regulated cell death process driven by lipid peroxidation, has emerged as a pivotal mechanism in mycotoxin-induced redox pathology. This review synthesizes the molecular interplay between fungal secondary metabolites (e.g., aflatoxin B1, deoxynivalenol) and ferroptotic pathways, revealing how mycotoxins subvert cellular iron homeostasis through transferrin receptor 1 (TfR1) upregulation and ferritinophagy-mediated iron release, while concurrently inactivating glutathione peroxidase 4 (GPX4) and depleting reduced glutathione. Through integrative analysis of tissue-specific toxicity profiles (hepatic > renal > intestinal), we propose a "two-hit" model wherein mycotoxin bioactivation synergizes with organ-specific ferroptosis vulnerability to drive pathological outcomes. Conversely, dietary interventions utilizing selenium-enriched compounds and polyphenolic antioxidants demonstrate dual protective mechanisms: chelating redox-active iron pools while preserving GPX4 activity and membrane phospholipid integrity. In addition, we evaluated the therapeutic strategies of intervening ferroptosis from food components to alleviate mycotoxin-induced pathology, providing a translational framework for innovation in livestock health and food safety.