In RCC cells harboring mutant versions of p53 and PTEN, the interplay of excessive ROS generation, impaired mitochondrial quality control, and deregulated apoptosis creates a unique vulnerability that can be exploited by agents such as olivomycin A. Thus, targeting the p53/PTEN-mitochondrial clearance axis may represent a promising therapeutic strategy for addressing aggressive RCC subtypes that are refractory to current treatments. Here, PTEN is linked to renal cell carcinoma.