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Fluxes in "free" and total zinc are essential for progression of intraerythrocytic stages of Plasmodium falciparum.
Title | Fluxes in "free" and total zinc are essential for progression of intraerythrocytic stages of Plasmodium falciparum. |
Publication Type | Journal Article |
Year of Publication | 2012 |
Authors | Marvin, RG, Wolford, JL, Kidd, MJ, Murphy, S, Ward, J, Que, EL, Mayer, ML, Penner-Hahn, JE, Haldar, K, O'Halloran, TV |
Journal | Chem Biol |
Volume | 19 |
Issue | 6 |
Pagination | 731-41 |
Date Published | 2012 Jun 22 |
ISSN | 1879-1301 |
Abstract | Dynamic 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. |
DOI | 10.1016/j.chembiol.2012.04.013 |
Alternate Journal | Chem. Biol. |
PubMed ID | 22726687 |
PubMed Central ID | PMC3601789 |
Grant List | AI39071 / AI / NIAID NIH HHS / United States GM038784 / GM / NIGMS NIH HHS / United States GM38047 / GM / NIGMS NIH HHS / United States HL078826 / HL / NHLBI NIH HHS / United States HL079397 / HL / NHLBI NIH HHS / United States HL69630 / HL / NHLBI NIH HHS / United States NCI CA060553 / CA / NCI NIH HHS / United States P01 HL078826 / HL / NHLBI NIH HHS / United States R01 AI039071 / AI / NIAID NIH HHS / United States R01 GM038047 / GM / NIGMS NIH HHS / United States R01 GM038784 / GM / NIGMS NIH HHS / United States R01 HL069630 / HL / NHLBI NIH HHS / United States R01 HL079397 / HL / NHLBI NIH HHS / United States R37 GM038784 / GM / NIGMS NIH HHS / United States |