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Metabolic immunity to infection is driven by mitochondrial one-carbon metabolism

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Paper Summary

Paperzilla title
ATF4: The Folate Gatekeeper That Starves *Toxoplasma*

This study demonstrates that the transcription factor ATF4 activates a mitochondrial metabolic defense against the parasite *Toxoplasma gondii* by increasing mitochondrial one-carbon metabolism, which uses folate, an essential B vitamin. This increased folate use restricts the parasite's access to folate, which is crucial for its own growth. In a mouse model, ATF4 activation was linked to a host-protective response.

Explain Like I'm Five

A protein called ATF4 helps our cells use a vitamin called folate to keep a parasite called *Toxoplasma gondii* from growing too much. It's like ATF4 is making our cells better at grabbing the folate so the parasite can't have it.

Possible Conflicts of Interest

None identified.

Identified Limitations

Generalizability
While the study demonstrates a mechanism in vitro and in a mouse model, its direct applicability to humans, or to the wide range of species Toxoplasma can infect, is unknown.
Focus on Folate Competition
The study focuses on the role of folate competition, but other nutrient dependencies or metabolic interactions could also play a role.

Rating Explanation

This study uses a clear methodology to explore a novel mechanism of metabolic immunity to Toxoplasma infection. The research is well-executed, providing compelling in vitro and in vivo data. The identification of ATF4 as a key regulator of this defense mechanism offers potential avenues for therapeutic intervention, although further research is needed to translate these findings into clinical applications.

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Topic Hierarchy

Domain: Life Sciences
Subfield: Parasitology

File Information

Original Title: Metabolic immunity to infection is driven by mitochondrial one-carbon metabolism
Uploaded: August 19, 2025 at 03:20 PM
Privacy: Public