Plasmodium cytochrome bc1 complex (mitochondrial complex III)

The Plasmodium cytochrome bc1 complex (mitochondrial complex III) is a key multi-subunit enzyme in the mitochondrial electron transport chain, responsible for transferring electrons from ubiquinol to cytochrome c and generating the proton gradient required for ATP synthase. It is essential for parasite survival in blood and mosquito stages and is structurally divergent from the human counterpart, making it an attractive and validated antimalarial drug target. Drugs such as atovaquone and CK-2-68 selectively inhibit this complex, often by binding to the quinol oxidation site of the cytochrome bc1 complex, thus blocking mitochondrial function and killing the parasite. Resistance can arise through mutations in subunits such as cytochrome b or the Rieske iron-sulfur protein. While inhibition in Plasmodium is generally well-tolerated in humans due to selectivity, insufficient specificity poses a mitochondria-related safety risk. The complex includes core subunits CYTB, cytochrome c1, the Rieske protein, and several parasite-specific proteins, making it a focus for ongoing antimalarial development[1][4][5][6].

Other names

Plasmodium mitochondrial complex IIIPlasmodium cytochrome bc1 complexCytochrome bc1 complex (in Plasmodium)PfCIII

Inhibition of electron transfer from ubiquinol to cytochrome c Disruption of the proton gradient and mitochondrial membrane potential Inhibition of ATP production Selective binding to quinol oxidation site to arrest electron transfer