Critical roles of the mitochondrial complex II in oocyst formation of rodent malaria parasite Plasmodium berghei.
It is generally accepted that the mitochondria play central roles in energy production of most eukaryotes. In contrast, it has been thought that Plasmodium spp., the causative agent of malaria, rely mainly on cytosolic glycolysis but not mitochondrial oxidative phosphorylation for energy production during blood stages. However, Plasmodium spp. possesses all genes necessary for the tricarboxylic acid (TCA) cycle and most of the genes for electron transport chain (ETC) enzymes. Therefore, it remains elusive whether oxidative phosphorylation is essential for the parasite survival. To elucidate the role of TCA metabolism and ETC in malaria parasites, we deleted the gene for flavoprotein (Fp) subunit, Pbsdha, one of four components of complex II, a catalytic subunit for succinate dehydrogenase activity. The Pbsdha(-) parasite grew normally at blood stages in mouse. In contrast, ookinete formation of Pbsdha(-) parasites in the mosquito stage was severely impaired. Finally, Pbsdha(-) ookinetes failed in oocyst formation, leading to complete malaria transmission blockade. These results suggest that malaria parasite may switch the energy metabolism from glycolysis to oxidative phosphorylation to adapt to the insect vector where glucose is not readily available for ATP production.
Department of Biomedical Chemistry, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Akina
A
Hino
Makoto
M
Hirai
Takeshi Q
TQ
Tanaka
Yoh-ichi
Y
Watanabe
Hiroyuki
H
Matsuoka
Kiyoshi
K
Kita
D000818:Animals; D030801:Animals, Genetically Modified; D042963:Electron Transport Complex II / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004734:Energy Metabolism; D004912:Erythrocytes / Q000469:parasitology; D005420:Flavoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D018390:Gene Targeting; D049452:Green Fluorescent Proteins / Q000378:metabolism; D008288:Malaria / Q000469:parasitology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D033661:Oocysts / Q000201:enzymology / Q000378:metabolism*; D010271:Parasites / Q000201:enzymology / Q000254:growth & development* / Q000472:pathogenicity; D010641:Phenotype; D010962:Plasmodium berghei / Q000201:enzymology / Q000254:growth & development* / Q000472:pathogenicity; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
D005420:Flavoproteins; D015800:Protozoan Proteins; D049452:Green Fluorescent Proteins; D042963:Electron Transport Complex II