Science (New York, N.Y.) · 2025
Mitochondria protect against an intracellular pathogen by restricting access to folate.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Medeiros Tânia Catarina, Ovciarikova Jana, Li Xianhe, Krueger Patrick, Bartsch Tim, Reato Silvia, Crow John C, Tellez Sutterlin Michelle, Martins Garcia Bruna, Rais Irina, Allmeroth Kira, Hartman Matías D, Denzel Martin S, Purrio Martin, Mesaros Andrea, Leung Kit-Yi, Greene Nicholas D E, Sheiner Lilach, Giavalisco Patrick, Pernas Lena
Аннотация
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.