Plasmodium falciparum Mitochondrial Electron Transport Chain Cytochrome bc1 Complex

The cytochrome bc1 complex (mitochondrial complex III) in Plasmodium falciparum is a critical component of the mitochondrial electron transport chain (ETC), essential for de novo pyrimidine synthesis and maintaining mitochondrial membrane potential. It transfers electrons from ubiquinol to cytochrome c, generating a proton gradient that drives ATP synthesis. While blood-stage parasites primarily rely on glycolysis for ATP, the ETC's role in recycling ubiquinone is vital for dihydroorotate dehydrogenase (DHOD) activity, essential for pyrimidine biosynthesis. The complex is composed of core subunits cytochrome b, cytochrome c1, and Rieske iron-sulfur protein. Its structural differences from mammalian counterparts make it an attractive target for antimalarial drugs like atovaquone and ELQs. Inhibition leads to parasite death by disrupting mitochondrial function. Although ATP synthase activity is dispensable, proper ETC function and ubiquinone recycling are indispensable for pyrimidine biosynthesis and parasite survival.

Inhibition of ubiquinone binding at cytochrome b, leading to disruption of electron transport and parasite death.