Plasmodium mitochondrial cytochrome bc₁ complex (bc₁ complex)

The Plasmodium mitochondrial cytochrome bc₁ complex, also known as Complex III, is a multi-subunit enzyme essential for the survival of malaria parasites during their erythrocytic and hepatic stages (Biagini et al., 2006). It facilitates the transfer of electrons from ubiquinol to cytochrome c, a process coupled to the translocation of protons across the inner mitochondrial membrane to maintain an electrochemical gradient (Fisher et al., 2020). In Plasmodium species, the primary physiological role of this complex is to regenerate the ubiquinone pool required by dihydroorotate dehydrogenase (DHODH), an essential enzyme for de novo pyrimidine biosynthesis (Painter et al., 2007). Because the parasite lacks the ability to salvage preformed pyrimidines from its host, inhibition of the bc₁ complex effectively starves the parasite of the building blocks needed for DNA and RNA synthesis. This complex is the primary target of the antimalarial drug atovaquone, which binds to the ubiquinol oxidation (Qo) site (Srivastava et al., 1997). However, the emergence of resistance through single-point mutations in the parasite's mitochondrial-encoded cytochrome b gene remains a significant clinical challenge (Kessl et al., 2007).

Other names

Ubiquinol-cytochrome c reductaseComplex IIIMitochondrial respiratory chain complex IIICytochrome bc1Plasmodium falciparum cytochrome bc1 complex

Inhibition of the ubiquinol oxidation (Qo) site or ubiquinone reduction (Qi) site within the cytochrome bc1 complex, which disrupts the mitochondrial electron transport chain, leads to the loss of mitochondrial membrane potential, and halts de novo pyrimidine biosynthesis by preventing the regeneration of the ubiquinone pool.