Artemisinin kills malaria parasites by damaging proteins and inhibiting the proteasome

Jessica L. Bridgford; Stanley C. Xie; Simon A. Cobbold; Charisse Flerida A. Pasaje; Susann Herrmann; Tuo Yang; David L. Gillett; Lawrence R. Dick; Stuart A. Ralph; Con Dogovski; Natalie J. Spillman; Leann Tilley

doi:10.1038/s41467-018-06221-1

Nature Communications (Sep 2018)

Artemisinin kills malaria parasites by damaging proteins and inhibiting the proteasome

Jessica L. Bridgford,
Stanley C. Xie,
Simon A. Cobbold,
Charisse Flerida A. Pasaje,
Susann Herrmann,
Tuo Yang,
David L. Gillett,
Lawrence R. Dick,
Stuart A. Ralph,
Con Dogovski,
Natalie J. Spillman,
Leann Tilley

Affiliations

Jessica L. Bridgford: Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne
Stanley C. Xie: Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne
Simon A. Cobbold: Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne
Charisse Flerida A. Pasaje: Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne
Susann Herrmann: Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne
Tuo Yang: Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne
David L. Gillett: Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne
Lawrence R. Dick: Oncology Clinical R&D, Takeda Pharmaceuticals International Co
Stuart A. Ralph: Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne
Con Dogovski: Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne
Natalie J. Spillman: Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne
Leann Tilley: Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne

DOI: https://doi.org/10.1038/s41467-018-06221-1
Journal volume & issue: Vol. 9, no. 1
pp. 1 – 9

Abstract

Read online

Artemisinin (ART) is a widely used antimalarial drug, but its mechanism of action is poorly understood. Here, Bridgford et al. show that ART kills parasites by a two-pronged mechanism, causing protein damage and compromising proteasome function, and that accumulation of proteasome substrates activates the ER stress response.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

About the journal