Xu Rui, Beatty Wandy L, Greigert Valentin, Witola William H, Sibley L David
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63130, USA.
Department of Pathobiology, University of Illinois Urbana-Champaign, Urbana, IL 61802, USA.
bioRxiv. 2023 Jun 27:2023.06.27.546703. doi: 10.1101/2023.06.27.546703.
is an obligate intracellular parasite with a highly reduced mitochondrion that lacks the TCA cycle and the ability to generate ATP, making the parasite reliant on glycolysis. Genetic ablation experiments demonstrated that neither of the two putative glucose transporters CpGT1 and CpGT2 were essential for growth. Surprisingly, hexokinase was also dispensable for parasite growth while the downstream enzyme aldolase was required, suggesting the parasite has an alternative way of obtaining phosphorylated hexose. Complementation studies in support a role for direct transport of glucose-6-phosphate from the host cell by the parasite transporters CpGT1 and CpGT2, thus bypassing a requirement for hexokinase. Additionally, the parasite obtains phosphorylated glucose from amylopectin stores that are released by the action of the essential enzyme glycogen phosphorylase. Collectively, these findings reveal that relies on multiple pathways to obtain phosphorylated glucose both for glycolysis and to restore carbohydrate reserves.
是一种专性细胞内寄生虫,其线粒体高度退化,缺乏三羧酸循环和产生ATP的能力,这使得该寄生虫依赖糖酵解。基因敲除实验表明,两个假定的葡萄糖转运蛋白CpGT1和CpGT2对其生长都不是必需的。令人惊讶的是,己糖激酶对寄生虫生长也不是必需的,而下游酶醛缩酶是必需的,这表明该寄生虫有另一种获得磷酸化己糖的途径。补充研究支持寄生虫转运蛋白CpGT1和CpGT2直接从宿主细胞转运6-磷酸葡萄糖的作用,从而绕过了对己糖激酶的需求。此外,该寄生虫从支链淀粉储存中获得磷酸化葡萄糖,这些支链淀粉是由必需酶糖原磷酸化酶的作用释放出来的。总的来说,这些发现揭示了该寄生虫依靠多种途径来获得磷酸化葡萄糖,用于糖酵解和恢复碳水化合物储备。