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Chlorogenic Acid Modulates PINK1-Parkin-Mediated Mitochondrial Quality Control in T-2 Toxin-Induced Thymic
Dongguang Guo1, Mingyan Chen1, Ruiyan Niu2
1School of Biological Engineering, Xinxiang University, Xinxiang 453000 Henan, China.
Abstract:
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.
Insights
T-2 toxin causes immune dysfunction by damaging mitochondria. While mitophagy is activated, it
Area of Science:
- Immunotoxicology
- Mitochondrial Biology
- Cellular Stress Responses
Background:
- T-2 toxin (T-2), a trichothecene, causes thymic injury and immune dysfunction.
- The role of mitochondria in T-2-induced immunotoxicity, beyond the ROS-NF-κB-NLRP3 axis, requires further elucidation.
Purpose of the Study:
- To investigate the role of mitochondrial damage and mitophagy in T-2 toxin-induced thymic injury.
- To explore the potential protective effects of chlorogenic acid (CGA) against T-2 toxicity.
Main Methods:
- Utilized murine and thymic epithelial cell models to study T-2 toxicity.
- Assessed mitochondrial damage, mitophagy activation (PINK1-Parkin pathway), reactive oxygen species (ROS) levels, and thymus index.
- Investigated the effect of mitophagy inhibition and CGA treatment, including its impact on the KEAP1/SIRT1/AMPKα1 network.
Main Results:
- T-2 toxin induced mitochondrial damage and activated PINK1-Parkin mitophagy, but this response was insufficient to maintain homeostasis.
- Inhibiting mitophagy exacerbated mitochondrial dysfunction and increased ROS levels.
- Chlorogenic acid (CGA) ameliorated thymic atrophy, enhanced mitophagy, and reduced oxidative, inflammatory, and apoptotic damage.
- CGA's protective effects involved modulating the KEAP1/SIRT1/AMPKα1 network and were dependent on PINK1.
Conclusions:
- Insufficient mitophagy is a critical factor in T-2 toxin-induced immunotoxicity.
- Chlorogenic acid acts as a mitochondria-targeted dietary modulator, offering protection against T-2 toxicity by enhancing mitochondrial quality control.
