Plasmodium falciparum mitochondrial electron transport chain and redox system (Pf-mETC/Redox)

The Plasmodium falciparum mitochondrial electron transport chain (mETC) and redox system are essential for the parasite's survival and its transmission from humans to mosquitoes (Nixon et al., 2013). In the asexual blood stages, the mETC primarily functions to provide electrons for dihydroorotate dehydrogenase (DHODH), which is required for de novo pyrimidine biosynthesis (Sheokand et al., 2024). However, during the development of gametocytes—the sexual stages of the parasite—the mitochondria undergo a significant metabolic shift, becoming more active and relying on oxidative phosphorylation for ATP production (MacRae et al., 2013). This transition involves the upregulation of respiratory complexes and the development of mitochondrial cristae, making the system a vulnerable target for transmission-blocking interventions (Evers et al., 2021). Key components include the cytochrome bc1 complex (Complex III), NADH dehydrogenase 2 (NDH2), and various antioxidant enzymes that protect the parasite from oxidative damage (Müller et al., 2004). Drugs like atovaquone and experimental inhibitors like endochin-like quinolones (ELQs) target these pathways, exploiting structural differences between the parasite and human mitochondrial machinery to achieve selective toxicity (Nixon et al., 2013).

Other names

Plasmodium falciparum mitochondrial respiratory chainPf-mETCPlasmodium falciparum mitochondrial redox systemPf-mtETCPlasmodium falciparum gametocyte mitochondria

Inhibition of the cytochrome bc1 complex, inhibition of dihydroorotate dehydrogenase, inhibition of NADH dehydrogenase 2, disruption of mitochondrial membrane potential, and induction of oxidative stress.