Cytochrome bc1 complex (Complex III) (Complex III)

The parasitic mitochondrial cytochrome bc1 complex, also known as Complex III, is a multi-subunit enzyme essential for the survival of protozoan parasites, including Plasmodium species [Biagini et al., 2006, DOI: 10.1016/j.ijp.2005.12.001]. Located in the inner mitochondrial membrane, it facilitates the transfer of electrons from ubiquinol to cytochrome c, a process that generates the electrochemical gradient necessary for ATP production [Hunte et al., 2000, DOI: 10.1016/S0960-9822(00)00311-6]. In many parasites, the complex serves a dual role: it maintains the mitochondrial membrane potential and recycles ubiquinone, which is a vital electron acceptor for dihydroorotate dehydrogenase (DHODH) in the de novo pyrimidine biosynthesis pathway [Painter et al., 2007, DOI: 10.1038/nature05690]. Because these parasites often lack the ability to salvage preformed pyrimidines, inhibition of the bc1 complex leads to a cessation of DNA synthesis and parasite death [Painter et al., 2007]. Therapeutic agents like atovaquone target the ubiquinol-binding (Qo) site of the complex, exploiting structural differences between the parasite and host enzymes to achieve selective toxicity [Srivastava et al., 1997, DOI: 10.1074/jbc.272.7.3961; DrugBank DB00703]. However, the clinical utility of such drugs is frequently challenged by the rapid emergence of resistance, typically caused by single-nucleotide polymorphisms in the mitochondrial-encoded cytochrome b gene [Korsinczky et al., 2000, DOI: 10.1128/AAC.44.8.2100-2108.2000].

Other names

Ubiquinol-cytochrome c reductasebc1 complexCytochrome c reductaseMitochondrial complex IIIParasitic mitochondrial cytochrome bc1 complex

Inhibition of the ubiquinol oxidation (Qo) site or the ubiquinone reduction (Qi) site within the cytochrome b subunit, disrupting the electron transport chain and the proton motive force.