Please use this identifier to cite or link to this item:
Title: Drug-induced permeabilization of parasite's digestive vacuole is a key trigger of programmed cell death in Plasmodium falciparum
Authors: Ch'ng, J.-H.
Liew, K.
Goh, A.S.-P.
Sidhartha, E. 
Tan, K.S.-W. 
Keywords: Chloroquine
Digestive vacuole
Lysosomal membrane permeabilization
Plasmodium falciparum
Programmed cell death
Issue Date: Oct-2011
Citation: Ch'ng, J.-H., Liew, K., Goh, A.S.-P., Sidhartha, E., Tan, K.S.-W. (2011-10). Drug-induced permeabilization of parasite's digestive vacuole is a key trigger of programmed cell death in Plasmodium falciparum. Cell Death and Disease 2 (10) : -. ScholarBank@NUS Repository.
Abstract: Having previously characterized chloroquine (CQ)-induced programmed cell death (PCD) hallmarks in the malaria parasite Plasmodium falciparum and delineating a pathway linking these features, the roles of non-classical mediators were investigated in this paper. It was shown that the later stages of this pathway are Ca2 +-dependent and transcriptionally regulated. Moreover, it was demonstrated for the first time that micromolar concentrations of CQ partially permeabilized the parasite's digestive vacuole (DV) membrane and that this important upstream event appears to precede mitochondrial dysfunction. This permeabilization of the DV occurred without rupture of the DV membrane and was reminiscent of lysosome-mediated cell death in mammalian cells. As such micromolar concentrations of CQ are found in the patient's plasma after initial CQ loading, this alludes to a clinically relevant antimalarial mechanism of the drug which has yet to be recognized. Furthermore, other 'non-antimalarial' lysosomotropic compounds were also shown to cause DV permeabilization, triggering PCD in both CQ-sensitive and -resistant parasites. These findings present new avenues for antimalarial developments, which induce DV destabilization to kill parasites. © 2011 Macmillan Publishers Limited.
Source Title: Cell Death and Disease
ISSN: 20414889
DOI: 10.1038/cddis.2011.97
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
There are no files associated with this item.


checked on Jun 8, 2023


checked on Jun 8, 2023

Page view(s)

checked on Jun 8, 2023

Google ScholarTM



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.