Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2003 Aug 21;424(6951):957-61.
doi: 10.1038/nature01813.

Artemisinins target the SERCA of Plasmodium falciparum

U Eckstein-Ludwig  1 , R J Webb, I D A Van Goethem, J M East, A G Lee, M Kimura, P M O'Neill, P G Bray, S A Ward, S Krishna
Affiliations

Artemisinins target the SERCA of Plasmodium falciparum

U Eckstein-Ludwig et al. Nature. .

Abstract

Artemisinins are extracted from sweet wormwood (Artemisia annua) and are the most potent antimalarials available, rapidly killing all asexual stages of Plasmodium falciparum. Artemisinins are sesquiterpene lactones widely used to treat multidrug-resistant malaria, a disease that annually claims 1 million lives. Despite extensive clinical and laboratory experience their molecular target is not yet identified. Activated artemisinins form adducts with a variety of biological macromolecules, including haem, translationally controlled tumour protein (TCTP) and other higher-molecular-weight proteins. Here we show that artemisinins, but not quinine or chloroquine, inhibit the SERCA orthologue (PfATP6) of Plasmodium falciparum in Xenopus oocytes with similar potency to thapsigargin (another sesquiterpene lactone and highly specific SERCA inhibitor). As predicted, thapsigargin also antagonizes the parasiticidal activity of artemisinin. Desoxyartemisinin lacks an endoperoxide bridge and is ineffective both as an inhibitor of PfATP6 and as an antimalarial. Chelation of iron by desferrioxamine abrogates the antiparasitic activity of artemisinins and correspondingly attenuates inhibition of PfATP6. Imaging of parasites with BODIPY-thapsigargin labels the cytosolic compartment and is competed by artemisinin. Fluorescent artemisinin labels parasites similarly and irreversibly in an Fe2+-dependent manner. These data provide compelling evidence that artemisinins act by inhibiting PfATP6 outside the food vacuole after activation by iron.

PubMed Disclaimer

Comment in

  • Malaria: to kill a parasite.
    Ridley RG. Ridley RG. Nature. 2003 Aug 21;424(6951):887-9. doi: 10.1038/424887a. Nature. 2003. PMID: 12931167 No abstract available.

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

Publication types

MeSH terms