In 5-fluorouracil (5-FU)-resistant CRC cells, mitochondrial-localized dihydroorotate dehydrogenase (DHODH) aberrantly translocates to the cytoplasm, resulting in two distinct effects: firstly, cytoplasmic DHODH catalyzes pyrimidine synthesis, forming a competitive antagonist against 5-FU; secondly, the loss of the mitochondrial lipid peroxidation defense mechanism significantly increases the cells' sensitivity to ferroptosis.64 The gene discussed is DHODH; the disease is colorectal carcinoma.