Role of Ferroptosis in the Redox Biology of Mycotoxins

Area of Science:

• Biochemistry
• Toxicology
• Cell Biology

Background:

• Ferroptosis, an iron-dependent regulated cell death, is implicated in mycotoxin-induced oxidative stress.
• Mycotoxins like aflatoxin B1 and deoxynivalenol disrupt cellular iron homeostasis and antioxidant defenses.

Purpose of the Study:

• To review the molecular mechanisms linking mycotoxins to ferroptosis.
• To explore tissue-specific toxicity and propose a "two-hit" model for mycotoxin pathology.
• To evaluate dietary interventions for mitigating mycotoxin-induced ferroptosis.

Main Methods:

• Literature review synthesizing molecular pathways.
• Analysis of tissue-specific toxicity data (hepatic, renal, intestinal).
• Evaluation of dietary compounds (selenium, polyphenols) as ferroptosis inhibitors.

Main Results:

• Mycotoxins upregulate transferrin receptor 1 (TfR1) and induce ferritinophagy, increasing labile iron.
• Mycotoxins inactivate glutathione peroxidase 4 (GPX4) and deplete glutathione, promoting lipid peroxidation.
• A "two-hit" model explains synergistic toxicity involving mycotoxin bioactivation and organ susceptibility.
• Selenium and polyphenols chelate iron, preserve GPX4 activity, and protect membrane integrity.

Conclusions:

• Mycotoxins induce ferroptosis through complex redox and iron dysregulation.
• Dietary interventions show promise in preventing mycotoxin-induced ferroptosis.
• Findings provide a framework for improving livestock health and food safety through ferroptosis modulation.