Fluxes in 'Free' and Total Zinc Are Essential for Progression of Intraerythrocytic Stages of Plasmodium falciparum
| Autor: | Rebecca G. Marvin, James E. Penner-Hahn, Kasturi Haldar, Sean C. Murphy, Matthew J. Kidd, Thomas V. O'Halloran, Janet L. Wolford, Emily L. Que, Jesse Ward, Meghan L. Mayer |
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| Jazyk: | angličtina |
| Předmět: |
Cell signaling
Erythrocytes Plasmodium falciparum Clinical Biochemistry chemistry.chemical_element Zinc Molecular Dynamics Simulation Mitochondrion Biology Biochemistry Article Structure-Activity Relationship 03 medical and health sciences 0302 clinical medicine Drug Discovery Food vacuole Humans Parasite hosting Molecular Biology 030304 developmental biology Membrane potential Pharmacology 0303 health sciences Dose-Response Relationship Drug General Medicine biology.organism_classification 3. Good health Cell biology chemistry Molecular Medicine 030217 neurology & neurosurgery Intracellular |
| Zdroj: | Chemistry & Biology. (6):731-741 |
| ISSN: | 1074-5521 |
| DOI: | 10.1016/j.chembiol.2012.04.013 |
| Popis: | SummaryDynamic fluxes in the concentration of ions and small molecules are fundamental features of cell signaling, differentiation, and development. Similar roles for fluxes in transition metal concentrations are less well established. Here, we show that massive zinc fluxes are essential in the infection cycle of an intracellular eukaryotic parasite. Using single-cell quantitative imaging, we show that growth of the blood-stage Plasmodium falciparum parasite requires acquisition of 30 million zinc atoms per erythrocyte before host cell rupture, corresponding to a 400% increase in total zinc concentration. Zinc accumulates in a freely available form in parasitophorous compartments outside the food vacuole, including mitochondria. Restriction of zinc availability via small molecule treatment causes a drop in mitochondrial membrane potential and severely inhibits parasite growth. Thus, extraordinary zinc acquisition and trafficking are essential for parasite development. |
| Databáze: | OpenAIRE |
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