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. Author manuscript; available in PMC: 2021 Sep 1.
Published in final edited form as: Cell Metab. 2020 Jul 14;32(3):341–352. doi: 10.1016/j.cmet.2020.06.019

Figure 3. DHODH Links the Mitochondrial ETC to Pyrimidine Synthesis.

Figure 3.

DHODH, a mitochondrial enzyme tethered to the inner mitochondrial membrane, converts dihydroorotate to orotate in the intermembrane space. DHODH donates two electrons to mitochondrial ubiquinone (CoQ) within the ETC. There are currently FDA-approved DHODH inhibitors used for rheumatoid arthritis like leflunomide, as well as other newer DHODH inhibitors. DHODH inhibition has shown promise in preclinical studies of cancer. Atomic structures: DHODH (PDB: 4LS1), complex III (PDB: 6Q9E) (Letts et al., 2019), cytochrome c (PDB: 2B4Z) (Mirkin et al., 2008), and complex IV (PDB: 5Z62) (Zong et al., 2018).