 Abstract ferroptosis is an eye-independent regulated cell death that suppresses tumor growth. It is activated by extensive peroxidation of membrane phospholipids caused by oxidative stress. GPX4, an antioxidant enzyme, reduces these peroxidized membrane phospholipids thereby inhibiting ferroptosis. This enzyme has two distinct subcellular localizations, the cytosol and mitochondria. Dihydrooritate dehydrogenase, DODE, complements mitochondrial GPX4 in reducing peroxidized membrane phospholipids. It is the rate-limiting enzyme in de novo pyrimidine nucleotide biosynthesis. Its role in ferroptosis inhibition suggests that DODE inhibitors could have two complementary mechanisms of action against tumors, inhibiting de novo pyrimidine nucleotide biosynthesis and enhancing ferroptosis. However, the link between mitochondrial function and ferroptosis and the involvement of DODE in the electron. This article was authored by Alvin Amos, Alex Amos, Lerong Wu, and others. We are article.tv, links in the description below.