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• W4220996945 abstract "The Plasmodium digestive vacuole (DV) is a unique parasite organelle dedicated to the consumption of host cell hemoglobin and the detoxification of heme. In situ studies are beginning to unravel the mechanistic basis of the parasite’s druggable heme biomineralization pathway. DV-associated lipids play essential roles in endocytic traffic, hemozoin nucleation, and membrane homeostasis. Transporters of the DV membrane mediate the exchange of ions and metabolites and modulate parasite drug susceptibility. During intraerythrocytic growth, the human malaria parasite Plasmodium falciparum degrades up to 80% of the host cell's hemoglobin inside an acidified organelle called the digestive vacuole (DV). Here, the globin chains are broken down by a number of proteases, while heme is detoxified through biomineralization, a process that is targeted by several potent antimalarial drugs. This review explores our current understanding of the DV, including the digestion of hemoglobin, the sequestration of heme, and the functions of lipids and transporters of the DV membrane. Furthermore, the mechanisms of drug action inside the DV and the molecular adaptations that mediate resistance are discussed. During intraerythrocytic growth, the human malaria parasite Plasmodium falciparum degrades up to 80% of the host cell's hemoglobin inside an acidified organelle called the digestive vacuole (DV). Here, the globin chains are broken down by a number of proteases, while heme is detoxified through biomineralization, a process that is targeted by several potent antimalarial drugs. This review explores our current understanding of the DV, including the digestion of hemoglobin, the sequestration of heme, and the functions of lipids and transporters of the DV membrane. Furthermore, the mechanisms of drug action inside the DV and the molecular adaptations that mediate resistance are discussed. heterocyclic aromatic compounds which often display antimalarial activity through inhibition of hemozoin formation. the relic plastid of the malaria parasite that is involved in biosynthesis of fatty acids, iron–sulfur clusters, heme, and isoprenoids. a plant-derived antimalarial that causes radical damage to the parasite following activation by heme iron. (synthetic) crystals consisting of cyclic hematin dimers. β-hematin and hemozoin are structurally identical. a 4-aminoquinoline previously used in antimalarial chemotherapy. It inhibits hemozoin formation. a transporter of the DVM that exports peptides and, in resistant parasite mutants, antimalarial drugs. a form of osmotic pressure induced by impermeable proteins. invaginations of the parasite’s two surrounding membranes with a narrow opening. Cytostomes are the site at which host cell cytosol is internalized by endocytosis. striation caused by constructive interference of waves from equally spaced slits, for example, different layers of a hemozoin crystal. a unique parasite organelle in which host cell hemoglobin is degraded and hemozoin is formed. interface between two crystallites in a polycrystalline solid. oxidation product of heme that contains iron in the ferric state. coordination complex of porphyrin and ferrous iron. Heme is a critical cofactor of various proteins, including hemoglobin. hematin crystals of biological origin. Hemozoin is generated in the Plasmodium digestive vacuole from hemoglobin-derived heme. Plasmodium kelch propeller protein involved in endocytosis and artemisinin resistance. a protein family characterized by an eight-stranded β-barrel, which is involved in binding and transport of various hydrophobic ligands. an enzyme catalyzing the hydrolysis of lysophosphatidylcholine to glycerophosphocholine and fatty acid. a triarylmethane dye used to stabilize and stain certain lipid structures in chemically fixed electron microscopy sections. an ABC transporter believed to import antimalarial drugs into the Plasmodium digestive vacuole. lipids that lack charged groups. Neutral lipids, such as di- and triacylglycerol, are often generated to conserve energy and membrane progenitors. spherical accumulations of neutral lipids juxtaposed to the parasite's digestive vacuole. a host-cell-derived membrane compartment surrounding the parasite during intracellular development. a parasite lipocalin that modulates hemozoin formation in the digestive vacuole. a phosphoinositide lipid regulating endosomal functions and membrane identity. macrophages in the mammalian spleen, liver, and bone marrow that degrade senescent erythrocytes. young parasite stage marking the onset of intraerythrocytic development. schizogony is a type of cell division in which multiple rounds of nuclear division are followed by concerted cytokinesis. Throughout this process, the parasite is referred to as a schizont. initial aggregation step in crystallization that occurs on an ordered surface. this neutral lipid accumulates in the neutral lipid bodies of Plasmodium blood stages and consists of glycerol esterified with three fatty acids. intraerythrocytic parasite stage characterized by rapid growth and biomass production. a heteromultimeric protein complex that pumps protons across biological membranes, energized by hydrolysis of adenosine triphosphate. a monomeric proton pump energized by the hydrolysis of pyrophosphate." @default.
• W4220996945 created "2022-04-03" @default.
• W4220996945 creator A5039553426 @default.
• W4220996945 date "2022-07-01" @default.
• W4220996945 modified "2023-09-27" @default.
• W4220996945 title "Plasmodium’s bottomless pit: properties and functions of the malaria parasite's digestive vacuole" @default.
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