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Journal article
Atovaquone, a Broad Spectrum Antiparasitic Drug, Collapses Mitochondrial Membrane Potential in a Malarial Parasite
The Journal of biological chemistry, v 272(7), pp 3961-3966
14 Feb 1997
PMID: 9020100
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
At present, approaches to studying mitochondrial functions in malarial parasites are quite limited because of the technical difficulties in isolating functional mitochondria in sufficient quantity and purity. We have developed a flow cytometric assay as an alternate means to study mitochondrial functions in intact erythrocytes infected with Plasmodium yoelii, a rodent malaria parasite. By using a very low concentration (2 nM) of a lipophilic cationic fluorescent probe, 3,3′dihexyloxacarbocyanine iodide, we were able to measure mitochondrial membrane potential(ΔΨm) in live intact parasitized erythrocytes through flow cytometry. The accumulation of the probe into parasite mitochondria was dependent on the presence of a membrane potential since inclusion of carbonyl cyanide m-chlorophenylhydrazone, a protonophore, dissipated the membrane potential and abolished the probe accumulation. We tested the effect of standard mitochondrial inhibitors such as myxothiazole, antimycin, cyanide and rotenone. All of them except rotenone collapsed the ΔΨm and inhibited respiration. The assay was validated by comparing the EC50 of these compounds for inhibiting ΔΨm and respiration. This assay was used to investigate the effect of various antimalarial drugs such as chloroquine, tetracycline and a broad spectrum antiparasitic drug atovaquone. We observed that only atovaquone collapsed ΔΨm and inhibited parasite respiration within minutes after drug treatment. Furthermore, atovaquone had no effect on mammalian ΔΨm. This suggests that atovaquone, shown to inhibit mitochondrial electron transport, also depolarizes malarial mitochondria with consequent cellular damage and death.
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Details
- Title
- Atovaquone, a Broad Spectrum Antiparasitic Drug, Collapses Mitochondrial Membrane Potential in a Malarial Parasite
- Creators
- Indresh K. Srivastava - From the ‡ Department of Microbiology and Immunology and theHagai Rottenberg - Allegheny University of the Health SciencesAkhil B. Vaidya - From the ‡ Department of Microbiology and Immunology and theAshok B Vaidya - Microbiology and Immunology
- Publication Details
- The Journal of biological chemistry, v 272(7), pp 3961-3966
- Publisher
- Elsevier
- Grant note
- AI28398 / National Institutes of Health AG13779 / A. B. V.
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:A1997WH01900016
- Scopus ID
- 2-s2.0-0031052025
- Other Identifier
- 991019169653504721
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- Web of Science research areas
- Biochemistry & Molecular Biology