Protozoan mitochondrial cytochrome bc1 complex (ubiquinone site) (bc1 complex)

The protozoan mitochondrial cytochrome bc1 complex, also known as Complex III, is a multi-subunit enzyme essential for the survival of various protozoan parasites, including Plasmodium species (Srivastava et al., 1997). It functions as a critical component of the electron transport chain, facilitating the transfer of electrons from ubiquinol to cytochrome c while pumping protons across the inner mitochondrial membrane. This process is vital not only for ATP production but also for maintaining the pool of ubiquinone required for de novo pyrimidine synthesis via dihydroorotate dehydrogenase (Painter et al., 2007). In many protozoa, the lack of a functional tricarboxylic acid cycle makes this complex a metabolic bottleneck. Therapeutic agents like atovaquone specifically target the ubiquinone binding sites, primarily the Qo site, of the cytochrome b subunit to inhibit parasite respiration (Korsinczky et al., 2000). This inhibition leads to a collapse of the mitochondrial membrane potential and subsequent parasite death. However, the clinical utility of such drugs is often challenged by the rapid emergence of resistance-conferring mutations within the mitochondrial genome, such as the Y268S mutation in Plasmodium falciparum (Birth et al., 2014). Research continues into next-generation inhibitors that target the Qi site to overcome existing resistance mechanisms.

Other names

Complex IIIUbiquinol-cytochrome c reductaseQo siteQi siteCytochrome b-c1 complex

Inhibition of electron transfer within the mitochondrial respiratory chain by binding to the ubiquinone binding sites (Qo or Qi), thereby disrupting the proton gradient and pyrimidine biosynthesis (Srivastava et al., 1997; Painter et al., 2007).