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

Ubiquinol-cytochrome c reductase, commonly referred to as Complex III or the cytochrome bc1 complex, is a vital multi-subunit enzyme situated within the inner mitochondrial membrane (UniProt P00156). It functions as a central component of the eukaryotic electron transport chain, facilitating the transfer of electrons from ubiquinol to cytochrome c (Wikipedia). This electron transfer is coupled with the translocation of protons from the mitochondrial matrix to the intermembrane space, contributing to the electrochemical gradient required for ATP production via the Q-cycle mechanism (PMID: 10651478). Beyond its role in energy metabolism, Complex III is a primary site for the generation of reactive oxygen species (ROS), which can influence cellular signaling and contribute to oxidative stress-related pathologies (PMID: 16609071). Mutations in the subunits of this complex, particularly the mitochondrially encoded cytochrome b, are linked to various metabolic and neuromuscular disorders, such as GRACILE syndrome and exercise intolerance (NIH MedlinePlus). In the context of therapeutics, Ubiquinol-cytochrome c reductase is a well-established target for antimalarial drugs like atovaquone, which exploits structural differences between human and Plasmodium enzymes to achieve selectivity (PubChem CID 2274). It is also a major target for agricultural fungicides, which inhibit the enzyme to prevent fungal growth (PMID: 22533531). Research continues to explore the potential of targeting this complex in cancer cells, which often exhibit altered mitochondrial metabolism (PMID: 30249615).

Other names

Cytochrome bc1 complexCoenzyme Q-cytochrome c reductaseUbiquinol-cytochrome c oxidoreductaseComplex IIIEC 1.10.2.2

Inhibition of the Q-cycle by binding to the Qo or Qi sites, thereby blocking electron transfer from ubiquinol to cytochrome c and disrupting the mitochondrial proton gradient (PMID: 10651478).