Cytochrome bc1 complex (Complex III) ubiquinone-binding sites (Complex III Qo/Qi)

The Mitochondrial electron transport chain Complex III, also known as the cytochrome bc1 complex, is a multi-subunit enzyme essential for cellular respiration (UniProt P00156). It facilitates the transfer of electrons from ubiquinol to cytochrome c while simultaneously pumping protons across the inner mitochondrial membrane to generate a proton motive force for ATP synthesis (Crofts, 2004). This process occurs via the Q-cycle mechanism, which involves two distinct ubiquinone-binding sites: the Qo site, located near the intermembrane space, and the Qi site, located near the matrix (Hunte et al., 2000). These sites are critical therapeutic targets, particularly in the treatment of parasitic infections like malaria, where the drug atovaquone selectively inhibits the parasite's Qo site (Srivastava et al., 1999). Inhibition of these sites disrupts the energy metabolism of the cell and can lead to the accumulation of reactive oxygen species, ultimately causing cell death (Fisher et al., 2020). While primarily targeted in pathogens, Complex III dysfunction is also implicated in human mitochondrial diseases and is being investigated as a potential target in cancer therapy to exploit metabolic dependencies.

Other names

Ubiquinol-cytochrome c reductaseMitochondrial Complex IIIbc1 complexQ-cycle sitesCytochrome b binding sitesCoenzyme Q-cytochrome c reductase

Inhibition of the Q-cycle by binding to the Qo (outer) or Qi (inner) sites on the cytochrome b subunit, which prevents the transfer of electrons from ubiquinol to the Rieske iron-sulfur protein and cytochrome c1, thereby halting the mitochondrial electron transport chain (Hunte et al., 2000; Crofts, 2004).