Mitochondrial oxygen consumption in asexual and sexual blood stages of the human malarial parasite, Plasmodium falciparum.
The two developmental stages of human malarial parasite Plasmodium falciparum, asexual and sexual blood stages, were continuously cultivated in vitro. Both asexual and sexual stages of the parasites were assayed for mitochondrial oxygen consumption by using a polarographic assay. The rate of oxygen consumption by both stages was found to be relatively low, and was not much different. Furthermore, the mitochondrial oxygen consumption by both stages was inhibited to various degrees by mammalian mitochondrial inhibitors that targeted each component of complexes I- IV of the respiratory system. The oxygen consumption by both stages was also affected by 5-fluoroorotate, a known inhibitor of enzyme dihydroorotate dehydrogenase of the pyrimidine pathway and by an antimalarial drug atovaquone that acted specifically on mitochondrial complex III of the parasite. Moreover, antimalarials primaquine and artemisinin had inhibitory effects on the oxygen consumption by both stages of the parasites. Our results suggest that P. falciparum in both developmental stages have functional mitochondria that operate a classical electron transport system, containing complexes I-IV, and linked to the pyrimidine biosynthetic pathway.
Krungkrai
J
J
Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. fmedjkk@md2.md.chula.ac.th
Burat
D
D
Kudan
S
S
Krungkrai
S
S
Prapunwattana
P
P
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004579:Electron Transport / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008018:Life Cycle Stages / Q000187:drug effects / Q000502:physiology; D008928:Mitochondria / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology*; D010963:Plasmodium falciparum / Q000254:growth & development* / Q000378:metabolism*; D013785:Thailand
D004791:Enzyme Inhibitors