Fluxes in "free" and total zinc are essential for progression of intraerythrocytic stages of plasmodium falciparum

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. O'Halloran*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)731-741
Number of pages11
JournalChemistry and Biology
Volume19
Issue number6
DOIs
StatePublished - Jun 22 2012

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

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