Ubiquinol-cytochrome c reductase (Complex III) (Complex III)

The fungal mitochondrial cytochrome bc1 reductase, also known as Complex III, is a multi-subunit enzyme essential for the mitochondrial electron transport chain (Source: Wikipedia: Cytochrome bc1 complex). It catalyzes 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 (Source: UniProt: P00163). This complex is a primary target for several classes of antifungal agents, most notably the strobilurins and atovaquone, which bind to the quinone-binding sites (Qo or Qi) (Source: PubMed: 12110613). By inhibiting this enzyme, these drugs disrupt energy production and increase the generation of reactive oxygen species, leading to fungal cell death (Source: NCBI: PMC3126121). In addition to its role in energy metabolism, the cytochrome bc1 complex is involved in maintaining the redox balance within the fungal cell. The inhibition of this target is particularly effective because it halts the growth of a wide range of fungal pathogens, including those affecting both human health and agriculture (Source: PubMed: 15630477). However, the therapeutic utility is often challenged by the rapid emergence of resistance, frequently mediated by single nucleotide polymorphisms such as the G143A mutation in the cytochrome b gene (Source: PubMed: 25100519). Furthermore, drug design must ensure high selectivity for the fungal enzyme over the human mitochondrial counterpart to avoid significant off-target toxicity (Source: PubMed: 11472535).

Other names

Ubiquinol-cytochrome c reductaseCytochrome bc1 complexComplex IIICoenzyme Q-cytochrome c reductaseFungal mitochondrial cytochrome bc1 reductase

Inhibition of ubiquinol oxidation at the Qo site or reduction at the Qi site of the cytochrome bc1 complex, disrupting the Q-cycle and preventing ATP synthesis.