Chlorogenic Acid Modulates PINK1–Parkin–Mediated Mitochondrial Quality Control in T-2 Toxin–Induced Thymic Immunotoxicity

T-2 toxin (T-2), a potent immunotoxic trichothecene, induces severe thymic injury and immune dysfunction. Building on our identification of the ROS-NF-κB-NLRP3 axis, mitochondrial involvement remains poorly understood. Using murine and thymic epithelial cell models, we show that T-2 induces mitochondrial damage, activating PINK1-Parkin-mediated mitophagy that is adaptive but insufficient to maintain mitochondrial homeostasis. Inhibition of mitophagy by 3-methyladenine or Parkin silencing further compromised mitochondrial membrane potential by ∼34% and ∼22% versus T-2, respectively, accompanied by elevated intracellular ROS levels. Chlorogenic acid (CGA) ameliorated thymic atrophy, as evidenced by a ∼62% increase in thymus index versus T-2, enhanced PINK1-Parkin mitophagy, and alleviated oxidative, inflammatory, and apoptotic damage. Mechanistically, CGA modulated the KEAP1/SIRT1/AMPKα1 network, linking redox regulation to mitochondrial quality control, and its protective effects were largely abolished by PINK1 knockdown. Collectively, these findings establish insufficient mitophagy as a key driver of T-2 immunotoxicity and support CGA as a mitochondria-targeted dietary modulator.