The TFAM-OGG1 axis mediates T-2 toxin-induced chondrocyte mitochondrial dysfunction and cartilage degeneration

T-2 toxin, a potent trichothecene mycotoxin, exposes humans to its toxicity through chronic ingestion of contaminated food. As a key environmental risk factor for cartilage damage, its precise mechanism of disrupting mitochondrial homeostasis in chondrocytes remains unclear. This study employed transcriptome sequencing to identify core targets and validated findings using both in vitro and in vivo models. We demonstrate that T-2 toxin and its metabolite HT-2 toxin suppress the expression of mitochondrial transcription factor A (TFAM) and 8-oxoguanine DNA glycosylase-1 (OGG1). This suppression reduces mitochondrial membrane potential (ΔΨm), accelerates reactive oxygen species (ROS) accumulation, and aggravates mitochondrial DNA (mtDNA) oxidative damage, culminating in mitochondrial dysfunction with consequent adenosine triphosphate (ATP) depletion. This bioenergetic collapse ultimately leads to chondrocyte death and articular tissue degeneration. These findings suggest that T-2 toxin impairs mitochondrial integrity through disruption of the TFAM-OGG1 functional axis, highlighting a potential mechanistic link and promising intervention strategy for cartilage damage caused by T-2 toxin.