Plasmodium digestive vacuole proteins (DV proteins)

The Plasmodium digestive vacuole (DV) is a specialized acidic organelle essential for the survival of the malaria parasite during its intraerythrocytic stage (Francis, S. E., et al. 1997. Annu Rev Microbiol). Within the DV, the parasite degrades host hemoglobin to obtain essential amino acids, a process mediated by a suite of enzymes including plasmepsins (aspartic proteases) and falcipains (cysteine proteases) (Wunderlich, J., et al. 2012. Int J Med Microbiol). A critical byproduct of this degradation is free heme (ferriprotoporphyrin IX), which is toxic to the parasite; to survive, the parasite detoxifies heme by sequestering it into an insoluble crystalline form called hemozoin (Egan, T. J. 2008. Drug Des Devel Ther). This pathway is the primary target for many classic antimalarial drugs, such as chloroquine and quinine, which interfere with hemozoin formation, leading to the accumulation of toxic heme and parasite death (Tilley, L., et al. 2016. Dalton Trans). Additionally, artemisinin-based compounds are activated by heme within the DV to produce free radicals that damage parasite membranes and proteins (Tilley, L., et al. 2016. Dalton Trans). The DV also contains transporters like PfCRT and PfMDR1, which are central to the development of drug resistance by modulating drug concentrations within the organelle (Wunderlich, J., et al. 2012. Int J Med Microbiol).

Other names

Heme detoxification pathwayHemoglobin degradation pathwayMalarial digestive vacuole enzymesHemozoin formation pathway

Inhibition of heme biocrystallization into hemozoin, leading to toxic heme accumulation; inhibition of hemoglobin-degrading proteases (plasmepsins and falcipains); and heme-mediated activation of endoperoxides to generate lethal free radicals.