Biogenesis of cytochromescandc₁in the electron transport chain of malaria parasites

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 1, 2024

malaria parasites retain an essential mitochondrional electron transport chain (ETC) that is critical for growth within humans and mosquitoes a key antimalarial drug target. ETC function requires cytochromes

Language: Английский

Unraveling mechanisms of iron acquisition in malaria parasites

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: May 14, 2024

ABSTRACT Plasmodium falciparum malaria parasites invade and multiply inside red blood cells (RBCs), the most iron-rich compartment in humans. Like all cells, P. requires nutritional iron to support essential metabolic pathways, but critical mechanisms of acquisition trafficking during RBC infection have remained obscure. Parasites internalize liberate massive amounts heme large-scale digestion hemoglobin within an acidic food vacuole (FV) lack a oxygenase release porphyrin-bound iron. Although FV is sequestered into inert hemozoin crystals, prior studies indicate that trace escapes biomineralization susceptible non-enzymatic degradation oxidizing environment labile retain homolog divalent metal transporter 1 (DMT1), known mammalian transporter, its role has not been tested. Our phylogenetic DMT1 (PfDMT1) retains conserved molecular features for transport. We localized this protein membrane defined orientation export-competent topology. Conditional knockdown PfDMT1 expression lethal parasites, which display broad cellular defects iron-dependent functions, including impaired apicoplast biogenesis mitochondrial polarization. are selectively rescued from partial by supplementation with exogenous iron, other metals. These results paradigm whereby gatekeeper blood-stage suggest therapeutic targeting may be potent antimalarial strategy.

Language: Английский

Dobinin K Displays Antiplasmodial Activity through Disruption of Plasmodium falciparum Mitochondria and Generation of Reactive Oxygen Species

Molecules, Journal Year: 2024, Volume and Issue: 29(19), P. 4759 - 4759

Published: Oct. 8, 2024

Dobinin K is a novel eudesmane sesquiterpenoids compound isolated from the root of

Language: Английский