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Title: Fluxes in ;Free; and Total Zinc Are Essential for Progression of Intraerythrocytic Stages of Plasmodium falciparum

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.

Authors:
; ; ; ; ; ; ; ; ; ;  [1];  [2];  [2];  [2]
  1. (Michigan)
  2. (
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
National Institutes of Health (NIH)
OSTI Identifier:
1049542
Resource Type:
Journal Article
Journal Name:
Chem. Biol.
Additional Journal Information:
Journal Volume: 19; Journal Issue: (6) ; 06, 2012
Country of Publication:
United States
Language:
ENGLISH
Subject:
37 INORGANIC, ORGANIC, PHYSICAL AND ANALYTICAL CHEMISTRY; 59 BASIC BIOLOGICAL SCIENCES; ATOMS; AVAILABILITY; COMPARTMENTS; ERYTHROCYTES; FOOD; MEMBRANES; MITOCHONDRIA; PARASITES; PLASMODIUM; TRANSITION ELEMENTS; ZINC

Citation Formats

Marvin, Rebecca G., Wolford, Janet L., Kidd, Matthew J., Murphy, Sean, Ward, Jesse, Que, Emily L., Mayer, Meghan L., Penner-Hahn, James E., Haldar, Kasturi, O, Halloran, Thomas V., UWASH), NWU), and Notre). Fluxes in ;Free; and Total Zinc Are Essential for Progression of Intraerythrocytic Stages of Plasmodium falciparum. United States: N. p., 2012. Web. doi:10.1016/j.chembiol.2012.04.013.
Marvin, Rebecca G., Wolford, Janet L., Kidd, Matthew J., Murphy, Sean, Ward, Jesse, Que, Emily L., Mayer, Meghan L., Penner-Hahn, James E., Haldar, Kasturi, O, Halloran, Thomas V., UWASH), NWU), & Notre). Fluxes in ;Free; and Total Zinc Are Essential for Progression of Intraerythrocytic Stages of Plasmodium falciparum. United States. doi:10.1016/j.chembiol.2012.04.013.
Marvin, Rebecca G., Wolford, Janet L., Kidd, Matthew J., Murphy, Sean, Ward, Jesse, Que, Emily L., Mayer, Meghan L., Penner-Hahn, James E., Haldar, Kasturi, O, Halloran, Thomas V., UWASH), NWU), and Notre). Tue . "Fluxes in ;Free; and Total Zinc Are Essential for Progression of Intraerythrocytic Stages of Plasmodium falciparum". United States. doi:10.1016/j.chembiol.2012.04.013.
@article{osti_1049542,
title = {Fluxes in ;Free; and Total Zinc Are Essential for Progression of Intraerythrocytic Stages of Plasmodium falciparum},
author = {Marvin, Rebecca G. and Wolford, Janet L. and Kidd, Matthew J. and Murphy, Sean and Ward, Jesse and Que, Emily L. and Mayer, Meghan L. and Penner-Hahn, James E. and Haldar, Kasturi and O and Halloran, Thomas V. and UWASH) and NWU) and Notre)},
abstractNote = {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},
journal = {Chem. Biol.},
number = (6) ; 06, 2012,
volume = 19,
place = {United States},
year = {2012},
month = {10}
}