Center for Tropical and Emerging Global Diseases, University of Georgia, Paul D. Coverdell Center, 500 D.W. Brooks Drive, Athens, GA 30602, USA.
Cell Host Microbe. 2010 Jan 21;7(1):62-73. doi: 10.1016/j.chom.2009.12.002. Epub 2009 Dec 31.
Apicomplexa are unicellular eukaryotic pathogens that carry a vestigial algal endosymbiont, the apicoplast. The physiological function of the apicoplast and its integration into parasite metabolism remain poorly understood and at times controversial. We establish that the Toxoplasma apicoplast membrane-localized phosphate translocator (TgAPT) is an essential metabolic link between the endosymbiont and the parasite cytoplasm. TgAPT is required for fatty acid synthesis in the apicoplast, but this may not be its most critical function. Further analyses demonstrate that TgAPT also functions to supply the apicoplast with carbon skeletons for additional pathways and, indirectly, with energy and reduction power. Genetic ablation of the transporter results in rapid death of parasites. The dramatic consequences of loss of its activity suggest that targeting TgAPT could be a viable strategy to identify antiparasitic compounds.
顶复门生物是带有退化的藻类内共生体(质体)的单细胞真核病原体。质体的生理功能及其与寄生虫代谢的整合仍知之甚少,有时甚至存在争议。我们证实,疟原虫质体膜定位的磷酸转运蛋白(TgAPT)是内共生体和寄生虫细胞质之间的一个重要代谢连接。TgAPT 是质体中脂肪酸合成所必需的,但这可能不是其最关键的功能。进一步的分析表明,TgAPT 还为质体提供了用于其他途径的碳骨架,并间接地为质体提供了能量和还原力。该转运蛋白的基因缺失会导致寄生虫迅速死亡。其活性丧失的巨大后果表明,靶向 TgAPT 可能是识别抗寄生虫化合物的可行策略。