Mitochondrial electron transport chain of Plasmodium falciparum (Pf-mtETC)

The mitochondrial electron transport chain (mtETC) of Plasmodium falciparum is a vital metabolic pathway and a major target for antimalarial drug development (Mather et al., 2007, PMID: 17503926). In the parasite's asexual blood stages, the mtETC's primary function is not the generation of ATP through oxidative phosphorylation, but rather the regeneration of ubiquinone (Painter et al., 2007, PMID: 17196537). This ubiquinone serves as an essential electron acceptor for dihydroorotate dehydrogenase (DHODH), a key enzyme in the de novo pyrimidine biosynthesis pathway required for DNA and RNA synthesis (Goodman et al., 2017, PMID: 28130421). The most clinically significant component is the Cytochrome bc1 complex (Complex III), which is targeted by the drug atovaquone (Biagini et al., 2006, PMID: 16461031). Disruption of the mtETC leads to the collapse of the mitochondrial membrane potential and the cessation of pyrimidine production, causing parasite death. Due to structural differences between Plasmodium and human mitochondrial complexes, this system provides a high degree of therapeutic selectivity.

Other names

Plasmodium falciparum mitochondrial respiratory chainPf-mtETCMalaria mitochondrial electron transport systemPlasmodium falciparum mitochondrial electron transport chain

Inhibition of the Cytochrome bc1 complex (Complex III) or other respiratory enzymes, leading to the depletion of the ubiquinone pool and subsequent inhibition of dihydroorotate dehydrogenase (DHODH), which halts pyrimidine biosynthesis (Painter et al., 2007; Biagini et al., 2006).