SIRT1/PGC-1α-regulated mitochondrial biogenesis is involved in T-2 toxin-induced chondrocyte injury.

T-2 toxin, a type A trichothecene mycotoxin, has been implicated as an environmental risk factor for Kashin-Beck disease (KBD), an endemic osteoarthropathy characterized by cartilage damage. However, whether T-2 toxin impairs mitochondrial biogenesis in chondrocytes and the underlying regulatory mechanism remain unclear. This study investigates the effects of T-2 toxin on mitochondrial function and biogenesis using in vivo and primary chondrocyte models and evaluated the involvement of the SIRT1/PGC-1α signaling pathway. T-2 toxin induced chondrocyte injury and mitochondrial dysfunction, as evidenced by ultrastructural mitochondrial abnormalities, loss of mitochondrial membrane potential (ΔΨm), and reduced mitochondrial DNA copy number (mtDNAcn). T-2 toxin also decreased Sirtuin 1 (SIRT1) protein expression, increased peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) acetylation, and downregulated proteins involved in mitochondrial biogenesis. Pharmacological activation of SIRT1 with resveratrol partially restored PGC-1α deacetylation and mitochondrial biogenesis and attenuated chondrocyte injury. These findings indicate that suppression of SIRT1/PGC-1α pathway contributes to T-2 toxin-induced impairment of mitochondrial biogenesis and chondrocyte injury. This study provides mechanistic evidence linking T-2 toxin exposure to defective mitochondrial biogenesis in chondrocytes and identifies the SIRT1/PGC-1α axis as a potential target for mitigating T-2 toxin-induced cartilage toxicity.