Erastin and celastrol instigates ATG5/ATG7-dependent autophagy, PINK1/Parkin-mediated mitophagy, and the induction of HSPs in an HSF1-dependent manner. The suppression of HSF1 further intensifies cell death in NSCLC cell lines HCC827, A540, and H1299, and impedes tumor proliferation in vivo. The gene discussed is PRKN; the disease is neoplasm.