A pyruvate transporter in the apicoplast of apicomplexan parasites

• 成果类型: Article
• 署名作者: Chen, Pu; Chen, Yukun; Xia, Ningbo; Fan, Bolin; Niu, Zhipeng; He, Zhengming; Wang, Xu; Yuan, Jing; Gupta, Nishith; Goldberg, Daniel; Shen, Bang
• 署名单位: Huazhong Agricultural University; Hubei Hongshan Laboratory; Xiamen University; Birla Institute of Technology & Science Pilani (BITS Pilani); Humboldt University of Berlin; Huazhong Agricultural University; Chinese Academy of Agricultural Sciences; Agriculture Genomes Institute at Shenzhen, CAAS
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-14665
• DOI: 10.1073/pnas.2314314121
• 发表日期: 2024-06-18
• 关键词: fatty-acid biosynthesis; toxoplasma-gondii; algal origin; protein; carrier; metabolism; organelle; identification; fosmidomycin; inhibition

摘要

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.