Plasmodium mitochondrial cytochrome bc1 complex

The Plasmodium mitochondrial cytochrome bc1 complex (complex III) is an essential multisubunit enzyme in the parasite's mitochondrial electron transport chain, responsible for transferring electrons from ubiquinol to cytochrome c and generating a proton gradient across the inner mitochondrial membrane, which supports ATP synthesis and is crucial for the oxidative recycling of ubiquinone. This function is vital for dihydroorotate dehydrogenase (DHODH) activity and de novo pyrimidine biosynthesis in Plasmodium, making the complex an established and validated antimalarial drug target. Inhibition of the bc1 complex by antimalarials such as atovaquone leads to blockade of electron transport, collapse of the mitochondrial membrane potential, and lethal impairment of pyrimidine synthesis pathways. Despite its validated target status, resistance often arises rapidly through point mutations in the cytochrome b subunit or via genetic changes affecting alternative metabolic pathways, which presents significant therapeutic challenges.

Other names

Plasmodium cytochrome bc1 complexPlasmodium complex IIIPlasmodium mitochondrial complex IIICytochrome bc1Cyt bc1

Inhibition of electron transfer from ubiquinol to cytochrome c, leading to collapse of mitochondrial membrane potential and block of de novo pyrimidine synthesis, causing parasite death. Competitive or non-competitive binding at quinone binding sites (Qo and Qi sites).