PDF(Pubmed)
Abstract：
Pyruvate lies at a pivotal node of carbon metabolism in eukaryotes. It is involved in diverse metabolic pathways in multiple organelles, and its interorganelle shuttling is crucial for cell fitness. Many apicomplexan parasites harbor a unique organelle called the apicoplast that houses metabolic pathways like fatty acid and isoprenoid precursor biosyntheses, requiring pyruvate as a substrate. However, how pyruvate is supplied in the apicoplast remains enigmatic. Here, deploying the zoonotic parasite Toxoplasma gondii as a model apicomplexan, we identified two proteins residing in the apicoplast membranes that together constitute a functional apicoplast pyruvate carrier (APC) to mediate the import of cytosolic pyruvate. Depletion of APC results in reduced activities of metabolic pathways in the apicoplast and impaired integrity of this organelle, leading to parasite growth arrest. APC is a pyruvate transporter in diverse apicomplexan parasites, suggesting a common strategy for pyruvate acquisition by the apicoplast in these clinically relevant intracellular pathogens.
摘要：
丙酮酸盐位于真核生物碳代谢的关键节点。它参与多种细胞器的多种代谢途径，它的细胞器间穿梭对细胞健康至关重要。许多牙尖丛寄生虫都有一种独特的细胞器，称为牙尖体，它容纳着脂肪酸和类异戊二烯前体生物合成等代谢途径，需要丙酮酸作为底物。然而,丙酮酸盐是如何在Apicoplast中提供的仍然是个谜。这里,部署人畜共患寄生虫弓形虫作为模型的顶部丛，我们鉴定了两种存在于生皮膜中的蛋白质,它们共同构成一种功能性的生皮膜丙酮酸载体(APC),以介导胞浆丙酮酸的输入.APC的耗竭会导致峰顶体中代谢途径的活性降低和细胞器的完整性受损。导致寄生虫生长停滞。APC是一种丙酮酸转运蛋白，存在于不同的顶丛寄生虫中，提示在这些临床相关的细胞内病原体中通过峰顶体获得丙酮酸的常见策略。
