Fluxes in "free" and Total Zinc Are Essential for Progression of Intraerythrocytic Stages of Plasmodium Falciparum

Overview

Journal Chem Biol

Publisher Elsevier

Specialties Biochemistry
Biology
Chemistry

Date 2012 Jun 26

PMID 22726687

Citations 27

Authors

Rebecca G Marvin

Janet L Wolford

Matthew J Kidd

Sean Murphy

Jesse Ward

Emily L Que

Meghan L Mayer

James E Penner-Hahn

Kasturi Haldar

Thomas V OHalloran

Affiliations

Soon will be listed here.

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.

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