Generation of ROS by SDHx mutations also leads to inhibition of prolyl hydroxylase, suggesting that increased ROS production mediates pseudo hypoxia in tumors with SDHx mutation and in hereditary leiomyomatosis and renal cell carcinoma in which FH-associated changes might develop in an HIF-dependent manner and with an Nrf2-associated antioxidant phenotype [40–43]. This evidence concerns the gene FH and hereditary clear cell renal cell carcinoma.