在这项工作中，该课题组发现激活转录因子4 （ATF4）激活了基于必需B族维生素叶酸的线粒体防御。在培养的哺乳动物细胞感染细胞内病原体刚地弓形虫时，ATF4通过驱动线粒体中叶酸主题的单碳代谢过程增加线粒体DNA水平。ATF4由宿主检测到寄生虫效应物诱导的线粒体应激触发，限制弓形虫获得合成单磷酸脱氧胸腺嘧啶所需的叶酸，从而限制寄生虫生长。然后，ATF4重新连接线粒体代谢，以建立基于叶酸的代谢防御弓形虫。
据介绍，作为细胞代谢物的主要消费者，线粒体随时准备与入侵的微生物竞争生长所需的营养物质。细胞是否利用线粒体代谢来保护自己免受感染尚不清楚。
附：英文原文
Title: Mitochondria protect against an intracellular pathogen by restricting access to folate
Author: Tania Catarina Medeiros, Jana Ovciarikova, Xianhe Li, Patrick Krueger, Tim Bartsch, Silvia Reato, John C. Crow, Michelle Tellez Sutterlin, Bruna Martins Garcia, Irina Rais, Kira Allmeroth, Matías D. Hartman, Martin S. Denzel, Martin Purrio, Andrea Mesaros, Kit-Yi Leung, Nicholas D. E. Greene, Lilach Sheiner, Patrick Giavalisco, Lena Pernas
Issue&Volume: 2025-08-14
Abstract: As major consumers of cellular metabolites, mitochondria are poised to compete with invading microbes for the nutrients that they need to grow. Whether cells exploit mitochondrial metabolism to protect from infection is unclear. In this work, we found that the activating transcription factor 4 (ATF4) activates a mitochondrial defense based on the essential B vitamin folate. During infection of cultured mammalian cells with the intracellular pathogen Toxoplasma gondii, ATF4 increased mitochondrial DNA levels by driving the one-carbon metabolism processes that use folate in mitochondria. Triggered by host detection of mitochondrial stress induced by parasite effectors, ATF4 limited Toxoplasma access to folates required for deoxythymidine monophosphate synthesis, thereby restricting parasite growth. Thus, ATF4 rewires mitochondrial metabolism to mount a folate-based metabolic defense against Toxoplasma.
DOI: adr6326
Source: https://www.science.org/doi/10.1126/science.adr6326