Ubiquinol-cytochrome c reductase (Mitochondrial electron transport chain complex III) (Complex III)

Mitochondrial electron transport chain complex III, also known as the cytochrome bc1 complex, is a multi-subunit enzyme essential for cellular respiration and energy production (UniProt, 2024). It catalyzes the transfer of electrons from ubiquinol to cytochrome c while simultaneously pumping protons across the inner mitochondrial membrane to generate an electrochemical gradient used for ATP synthesis (Crofts, 2004). The complex operates via the Q-cycle mechanism, which involves two distinct binding sites: the Qo site (where ubiquinol is oxidized) and the Qi site (where ubiquinone is reduced) (Fisher et al., 2020). This target is a critical site for pharmacological intervention, particularly in the treatment of parasitic and fungal infections (PubChem, 2024). For example, the antimalarial drug atovaquone targets the Qo site of the Plasmodium falciparum complex, leading to a collapse of the mitochondrial membrane potential and inhibition of de novo pyrimidine synthesis (Srivastava et al., 1999). In agriculture, strobilurin fungicides target the same site to prevent fungal growth on crops (Fisher et al., 2020). Therapeutic challenges include achieving high selectivity to avoid inhibiting human complex III, which could lead to host toxicity (Fisher et al., 2020). Additionally, the emergence of resistance mutations in the cytochrome b subunit remains a significant concern in clinical and agricultural settings (Fisher et al., 2020).

Other names

Cytochrome bc1 complexCoenzyme Q-cytochrome c oxidoreductasebc1 complexMitochondrial electron transport chain complex III Q-siteQ-site of complex III

Inhibition of the Q-cycle by binding to the ubiquinol oxidation (Qo) or ubiquinone reduction (Qi) sites, blocking electron transfer to cytochrome c and disrupting the proton gradient.