Mitochondrial homeostasis dysfunctions during the epithelial-mesenchymal transition process in lens epithelial cells.

Lens epithelial cells (LECs), the main mitochondria-containing cells in the lens, play a vital role in maintaining lens transparency. Mitochondrial homeostasis is essential for cellular function, yet its changes during epithelial-mesenchymal transition (EMT) in LECs remain unclear. In this study, EMT was induced in LECs using transforming growth factor-β2 (TGF-β2), and mitochondrial function was evaluated through ROS, ATP levels, membrane potential, Mitotracker staining, and electron microscopy. TGF-β2 treatment resulted in mitochondrial dysfunction, evidenced by increased ROS, decreased ATP production, and reduced membrane potential. Mitochondria changed from elongated tubular shapes to fragmented spherical forms. Mitochondrial dynamics were disrupted, with downregulation of fusion proteins (Mfn1, Mfn2, Opa1) and upregulation of fission protein Drp1. Mitophagy was impaired despite activation of the PINK1/Parkin pathway, and mitochondrial biogenesis was suppressed, as shown by decreased expression of PGC-1α and TFAM and reduced mtDNA copy number. These findings highlight a significant imbalance in mitochondrial homeostasis during TGF-β2-induced EMT in LECs, which may contribute to lens opacity and fibrotic cataract formation, offering potential targets for therapeutic intervention.