Mitochondrial fission is induced by increased ROS production and mitochondrial membrane potential abrogation, driving PTEN-induced kinase 1 (PINK1)/Parkin-dependent mitophagy and ferroptosis in non-small-cell lung cancer (NSCLC) cells, thus enhancing the anticancer effect of celastrol51. Here, PRKN is linked to non-small cell lung carcinoma.