Cytochrome bc1 complex, Qo site of cytochrome b (Complex III Qo site)

The Qo site of the cytochrome bc1 complex (Complex III) is a critical catalytic pocket located on the cytochrome b subunit, oriented toward the intermembrane space of the mitochondria (Source: UniProt P00156). It plays a central role in the Q-cycle by facilitating the oxidation of ubiquinol to ubiquinone, which is coupled to the translocation of protons across the inner mitochondrial membrane and the transfer of electrons to the Rieske iron-sulfur protein (Source: PubMed PMID: 10940040). This site is a major therapeutic target for antiparasitic agents, most notably atovaquone, which is used to treat malaria and toxoplasmosis by disrupting the parasite's mitochondrial electron transport chain (Source: StatPearls, Atovaquone). Additionally, the Qo site is the primary target for a large class of agricultural fungicides known as strobilurins (Source: PubMed PMID: 15590574). Clinical challenges associated with this target include the rapid emergence of resistance, often driven by single-point mutations in the cytochrome b gene, such as the Y268S mutation in Plasmodium falciparum (Source: PubMed PMID: 12414974). Because the bc1 complex is conserved across eukaryotes, drug design must focus on achieving high selectivity for the pathogen's Qo site over the human ortholog to minimize host toxicity.

Other names

Ubiquinol-cytochrome c reductaseComplex IIIQo siteOuter quinol oxidation siteCytochrome b Qo pocket

Inhibition of ubiquinol oxidation at the Qo site of the cytochrome bc1 complex, which prevents electron transfer to the Rieske iron-sulfur protein and cytochrome c1, thereby halting the mitochondrial electron transport chain and collapsing the membrane potential (Source: PubMed PMID: 10940040).