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顶复门寄生虫类质体中的丙酮酸转运蛋白。

A pyruvate transporter in the apicoplast of apicomplexan parasites.

机构信息

National Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, Hubei Province, People's Republic of China.

Hubei Hongshan Laboratory, Wuhan 430070, Hubei Province, People's Republic of China.

出版信息

Proc Natl Acad Sci U S A. 2024 Jun 18;121(25):e2314314121. doi: 10.1073/pnas.2314314121. Epub 2024 Jun 12.

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 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

丙酮酸位于真核生物碳代谢的关键节点。它参与多种细胞器中的多种代谢途径,其细胞器间穿梭对细胞活力至关重要。许多顶复门寄生虫拥有一种独特的细胞器,称为质体,其中包含脂肪酸和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,质体中丙酮酸的供应方式仍然是个谜。在这里,我们以人畜共患寄生虫 作为模型顶复门寄生虫,鉴定出两种位于质体膜上的蛋白质,它们共同构成了一种功能性的质体丙酮酸载体 (APC),以介导细胞质丙酮酸的输入。APC 的耗竭导致质体中代谢途径的活性降低,以及该细胞器完整性受损,导致寄生虫生长停滞。APC 是多种顶复门寄生虫中的丙酮酸转运蛋白,这表明质体获取丙酮酸的一种常见策略存在于这些临床上相关的细胞内病原体中。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bad1/11194499/5517778eda99/pnas.2314314121fig01.jpg

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