The malaria digestive vacuole.

ABSTRACT

During the development of malaria parasites within human erythrocytes, the fusion of digestive vesicles gives rise to a large digestive vacuole (DV). This organelle, which is maintained at low pH, processes 60-80 percent of the erythrocyte hemoglobin to provide a pool of amino acids that is crucial for parasite growth and development. During proteolysis, heme is released from hemoglobin as a toxic byproduct and is detoxified by biocrystallization to hemozoin. Proteases that contribute to hemoglobin breakdown, as well as other DV-associated proteins, arrive at this site via several different transport pathways. Antimalarial quinoline drugs, such as chloroquine, act by binding to heme and thus prevent its sequestration into hemozoin. Other drugs, such as artemisinin, may cause oxidative damage of DV macromolecules and membranes. The membrane of the DV contains ion pumps and transporters that maintain its low pH but are also pivotal in the development of parasite resistance to several antimalarial drugs. Methods for the isolation of the DV organelle have been developed to study the biogenesis and function of this important organelle.