TY - JOUR
T1 - Fluxes in "free" and total zinc are essential for progression of intraerythrocytic stages of plasmodium falciparum
AU - Marvin, Rebecca G.
AU - Wolford, Janet L.
AU - Kidd, Matthew J.
AU - Murphy, Sean
AU - Ward, Jesse
AU - Que, Emily L.
AU - Mayer, Meghan L.
AU - Penner-Hahn, James E.
AU - Haldar, Kasturi
AU - O'Halloran, Thomas V.
N1 - Funding Information:
This work was supported by the National Institutes of Health (Grant GM038784 to T.V.O.; Grant GM38047 to J.E.P.-H.; and Grants AI39071, HL078826, HL69630, and HL079397 to K.H.). Use of the Advanced Photon Source at Argonne National Laboratory was supported by the U.S. Department of Energy, with a special thanks to Stefan Vogt and Lydia Finney for their assistance with data analysis. ICP-MS metal analysis and confocal microscopy were performed at the Northwestern University Quantitative Bioelemental Imaging Center, generously supported by Grant NNA04CC36G from the National Aeronautics and Space Administration. Flow cytometric analysis was performed in the Northwestern University Flow Cytometry Facility, supported by Grant NCI CA060553 to the Northwestern Robert H. Lurie Comprehensive Cancer Center.
PY - 2012/6/22
Y1 - 2012/6/22
N2 - 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.
AB - 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.
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U2 - 10.1016/j.chembiol.2012.04.013
DO - 10.1016/j.chembiol.2012.04.013
M3 - Article
C2 - 22726687
AN - SCOPUS:84862751011
VL - 19
SP - 731
EP - 741
JO - Cell Chemical Biology
JF - Cell Chemical Biology
SN - 2451-9448
IS - 6
ER -