Plasmodium falciparum mitochondrial membrane potential (MMP)

The mitochondrial membrane potential (MMP) in Plasmodium falciparum is a critical electrochemical gradient generated by the mitochondrial electron transport chain (mETC) across the inner mitochondrial membrane (Mather et al., 2007). Unlike human mitochondria, which primarily utilize this gradient for ATP synthesis via oxidative phosphorylation, the malaria parasite relies on the mETC mainly to regenerate the ubiquinone pool (Painter et al., 2007). This pool is essential for the activity of dihydroorotate dehydrogenase (DHODH), a key enzyme in the de novo pyrimidine biosynthesis pathway required for DNA and RNA production (Biagini et al., 2006). Disruption of the mETC by antimalarial drugs, such as atovaquone, leads to the rapid collapse of the MMP (Srivastava et al., 1997). This collapse halts pyrimidine synthesis, ultimately leading to parasite death during the erythrocytic stage of infection (Mather et al., 2007). Because of its central role in parasite survival, the maintenance of MMP is a major focus of drug discovery, although it is a physiological state maintained by multiple enzymes rather than a single molecular target itself (Biagini et al., 2006).

Other names

Mitochondrial electrochemical gradientMitochondrial Delta-psi-mMitochondrial transmembrane potential

Inhibition of the mitochondrial electron transport chain (mETC) complexes, such as the Cytochrome bc1 complex, prevents proton pumping and leads to the dissipation of the electrochemical gradient (membrane potential), which is essential for the function of dihydroorotate dehydrogenase (DHODH) in pyrimidine biosynthesis (Mather et al., 2007; Painter et al., 2007).