Department of Biomedical Chemistry, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
J Biochem. 2012 Sep;152(3):259-68. doi: 10.1093/jb/mvs058. Epub 2012 May 23.
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.
人们普遍认为，线粒体在大多数真核生物的能量产生中起着核心作用。相比之下，人们一直认为疟原虫是疟疾的病原体，主要依赖细胞质糖酵解而不是线粒体氧化磷酸化来产生能量，而不是在血阶段。然而，疟原虫拥有三羧酸（TCA）循环所需的所有基因，以及电子传递链（ETC）酶的大部分基因。因此，氧化磷酸化是否对寄生虫的生存至关重要仍然难以捉摸。为了阐明 TCA 代谢和 ETC 在疟原虫中的作用，我们删除了编码黄素蛋白（Fp）亚基的基因，即复合物 II 的四个组成部分之一，琥珀酸脱氢酶活性的催化亚基 Pbsdha。Pbsdha(-)寄生虫在小鼠的血液阶段正常生长。相比之下，Pbsdha(-)寄生虫在蚊子阶段的动合子形成受到严重损害。最后，Pbsdha(-)动合子不能形成卵囊，导致疟疾传播完全阻断。这些结果表明，疟原虫可能会将能量代谢从糖酵解切换到氧化磷酸化，以适应昆虫媒介，在那里葡萄糖不易用于 ATP 产生。
