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Homeostatic Control of an Iron Repressor in a GI Tract Resident

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Journal Elife
Specialty Biology
Date 2023 May 25
PMID 37227051
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Abstract

The transition metal iron plays a crucial role in living cells. However, high levels of iron are potentially toxic through the production of reactive oxygen species (ROS), serving as a deterrent to the commensal fungus for colonization in the iron-rich gastrointestinal tract. We observe that the mutant lacking an iron-responsive transcription factor Hap43 is hyper-fit for colonization in murine gut. We demonstrate that high iron specifically triggers multiple post-translational modifications and proteasomal degradation of Hap43, a vital process guaranteeing the precision of intestinal ROS detoxification. Reduced levels of Hap43 de-repress the expression of antioxidant genes and therefore alleviate the deleterious ROS derived from iron metabolism. Our data reveal that Hap43 functions as a negative regulator for oxidative stress adaptation of to gut colonization and thereby provide a new insight into understanding the interplay between iron homeostasis and fungal commensalism.

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PMID: 37891489 PMC: 10612253. DOI: 10.1186/s12866-023-03069-4.

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