Seattle Biomedical Research Institute, 307 Westlake Avenue North, Suite 500, Seattle, WA 98109, USA.
Mol Microbiol. 2010 Feb;75(4):957-71. doi: 10.1111/j.1365-2958.2009.07034.x.
Plasmodium parasites possess a single pyruvate dehydrogenase (PDH) enzyme complex that is localized to the plastid-like organelle known as the apicoplast. Unlike most eukaryotes, Plasmodium parasites lack a mitochondrial PDH. The PDH complex catalyses the conversion of pyruvate to acetyl-CoA, an important precursor for the tricarboxylic acid cycle and type II fatty acid synthesis (FAS II). In this study, using a rodent malaria model, we show that the PDH E1 alpha and E3 subunits colocalize with the FAS II enzyme FabI in the apicoplast of liver stages but are not significantly expressed in blood stages. Deletion of the E1 alpha or E3 subunit genes of Plasmodium yoelii PDH caused no defect in blood stage development, mosquito stage development or early liver stage development. However, the gene deletions completely blocked the ability of the e1 alpha(-) and e3(-) parasites to form exo-erythrocytic merozoites during late liver stage development, thus preventing the initiation of a blood stage infection. This phenotype is similar to that observed for deletions of genes involved in FAS II elongation. The data strongly support the hypothesis that the sole role of PDH is to provide acetyl-CoA for FAS II.
疟原虫寄生虫拥有一种单一的丙酮酸脱氢酶（PDH）酶复合物，该复合物定位于被称为类质体的类质体样细胞器中。与大多数真核生物不同，疟原虫寄生虫缺乏线粒体 PDH。PDH 复合物催化丙酮酸转化为乙酰辅酶 A，这是三羧酸循环和 II 型脂肪酸合成（FAS II）的重要前体。在这项研究中，我们使用啮齿动物疟疾模型表明，PDH E1 alpha 和 E3 亚基与 FAS II 酶 FabI 在肝期的类质体中共定位，但在血期不显著表达。敲除疟原虫 PDH 的 E1 alpha 或 E3 亚基基因不会导致血期发育、蚊期发育或早期肝期发育缺陷。然而，基因缺失完全阻止了 e1 alpha(-)和 e3(-)寄生虫在晚期肝期发育过程中形成外红细胞裂殖子的能力，从而阻止了血液期感染的开始。这种表型与 FAS II 伸长过程中涉及的基因缺失所观察到的表型相似。这些数据强烈支持 PDH 的唯一作用是为 FAS II 提供乙酰辅酶 A 的假设。
