Toward understanding the role of mitochondrial complex II in the intraerythrocytic stages of Plasmodium falciparum: gene targeting of the Fp subunit.
Malaria parasites in human hosts depend on glycolysis for most of their energy production, and the mitochondrion of the intraerythrocytic form is acristate. Although the genes for all tricarboxylic acid (TCA) cycle members are found in the parasite genome, the presence of a functional TCA cycle in the intraerythrocytic stage is still controversial. To elucidate the physiological role of Plasmodium falciparum mitochondrial complex II (succinate-ubiquinone reductase (SQR) or succinate dehydrogenase (SDH)) in the TCA cycle, the gene for the flavoprotein subunit (Fp) of the enzyme, pfsdha (P.falciparum gene for SDH subunit A, PlasmoDB ID: PF3D7_1034400) was disrupted. SDH is a well-known marker enzyme for mitochondria. In the pfsdha disruptants, Fp mRNA and polypeptides were decreased, and neither SQR nor SDH activity of complex II was detected. The suppression of complex II caused growth retardation of the intraerythrocytic forms, suggesting that complex II contributes to intraerythrocytic parasite growth, although it is not essential for survival. The growth retardation in the pfsdha disruptant was rescued by the addition of succinate, but not by fumarate. This indicates that complex II functions as a quinol-fumarate reductase (QFR) to form succinate from fumarate in the intraerythrocytic parasite.
Department of Biomedical Chemistry, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Takeshi Q
TQ
Tanaka
Makoto
M
Hirai
Yoh-ichi
Y
Watanabe
Kiyoshi
K
Kita
D000818:Animals; D015415:Biomarkers; D042963:Electron Transport Complex II / Q000502:physiology*; D005650:Fumarates; D005786:Gene Expression Regulation / Q000502:physiology*; D018390:Gene Targeting; D009154:Mutation; D010963:Plasmodium falciparum / Q000166:cytology / Q000378:metabolism*; D021122:Protein Subunits; D013379:Substrate Specificity; D019802:Succinic Acid
D015415:Biomarkers; D005650:Fumarates; D021122:Protein Subunits; D019802:Succinic Acid; D042963:Electron Transport Complex II