T-2 toxin induces mitochondrial dysfunction in chondrocytes via the p53-cyclophilin D pathway

Area of Science:

• Biochemistry
• Cell Biology
• Toxicology

Background:

• Kashin-Beck disease is an endemic joint disorder linked to T-2 toxin exposure.
• Chondrocyte necrosis is a hallmark of the disease, suggesting cellular damage mechanisms require investigation.

Purpose of the Study:

• To elucidate the mechanism by which T-2 toxin induces mitochondrial dysfunction in chondrocytes.
• To investigate the role of the p53-cyclophilin D (CypD) pathway in T-2 toxin-induced chondrocyte damage.

Main Methods:

• GeneCards analysis identified the p53 signaling pathway in T-2 toxin response.
• Upregulation of p53 and p53-CypD complex was assessed in rat cartilage and ATDC5 cells.
• Transmission electron microscopy evaluated mitochondrial structure, and mitochondrial function was assessed via membrane potential and ROS generation.

Main Results:

• T-2 toxin exposure upregulated p53 protein and the p53-CypD complex in chondrocytes.
• Mitochondrial damage, including mPTP opening, decreased membrane potential, and increased ROS, was observed.
• Inhibition of p53 using Pifithrin-α mitigated T-2 toxin-induced mitochondrial dysfunction.

Conclusions:

• T-2 toxin activates p53, which translocates to mitochondria, complexes with CypD, and triggers mitochondrial dysfunction.
• The p53-CypD interaction mediates excessive mPTP opening, leading to chondrocyte apoptosis in Kashin-Beck disease.
• Targeting the p53-CypD pathway may offer therapeutic strategies for T-2 toxin-induced joint disease.