Fig. 2
DHODH and mitochondrial respiratory chain. The mammalian mitochondrial electron transport chain comprises four enzyme complexes located in the mitochondrial inner membrane: complexes I, II, III, and IV. Complexes I and II transfer reducing equivalents from NADH and succinate to complex III via the ubiquinone pool, respectively, and complex III further transfers these equivalents to complex IV through cytochrome c. Electrons from complex IV are eventually transferred to dioxygen, subsequently producing water. ATP synthase generates ATPs by oxidative phosphorylation utilizing the transmembrane electrochemical gradient maintained by proton pumping activities of complexes I, III, and IV [36]. DHODH converts dihydroorotate to orotate, generating electrons that are transferred via redox-cycling of ubiquinone to complex III [2]. Thus, the de novo synthesis of pyrimidine nucleotides is coupled to the mitochondrial respiratory chain via DHODH [47]. Abbreviations: CI, complex I; CII, complex II; CIII, complex III; CIV, complex IV; CV, complex IV; FAD, flavin adenine dinucleotide; FMN, flavin mononucleotide. Q, coenzyme Q (CoQ), so known as ubiquinone; QH2, the hydroquinone (antioxidant) form of CoQ, also known as ubiquinol; UMP, uridine monophosphate