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Yeast Model Uncovers Dual Roles of Mitochondria in the Action of Artemisinin

Summary: Yeast Model Uncovers Dual Roles
of Mitochondria in the Action of Artemisinin
Wei Li1
, Weike Mo1
, Dan Shen1
, Libo Sun1
, Juan Wang1
, Shan Lu1
, Jane M. Gitschier2
, Bing Zhou1*
1 The State Key Laboratory of Biomembrane and Membrane Biotechnology, Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing, China,
2 Departments of Medicine and Pediatrics and Howard Hughes Medical Institute, University of California, San Francisco, California, United States of America
Artemisinins, derived from the wormwood herb Artemisia annua, are the most potent antimalarial drugs currently
available. Despite extensive research, the exact mode of action of artemisinins has not been established. Here we use
yeast, Saccharamyces cerevisiae, to probe the core working mechanism of this class of antimalarial agents. We
demonstrate that artemisinin's inhibitory effect is mediated by disrupting the normal function of mitochondria
through depolarizing their membrane potential. Moreover, in a genetic study, we identify the electron transport chain
as an important player in artemisinin's action: Deletion of NDE1 or NDI1, which encode mitochondrial NADH
dehydrogenases, confers resistance to artemisinin, whereas overexpression of NDE1 or NDI1 dramatically increases
sensitivity to artemisinin. Mutations or environmental conditions that affect electron transport also alter host's


Source: Arnold, Jonathan - Nanoscale Science and Engineering Center & Department of Genetics, University of Georgia


Collections: Biotechnology