The vacuolar iron transporter mediates iron detoxification in Toxoplasma gondii

Dana Aghabi, Megan Sloan, Grace Gill, Elena Hartmann, Olga Antipova, Zhicheng Dou, Alfredo J. Guerra, Vern B. Carruthers and Clare R. Harding ()
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Dana Aghabi: University of Glasgow
Megan Sloan: University of Glasgow
Grace Gill: University of Glasgow
Elena Hartmann: University of Glasgow
Olga Antipova: Argonne National Laboratory
Zhicheng Dou: Clemson University
Alfredo J. Guerra: University of Michigan
Vern B. Carruthers: University of Michigan
Clare R. Harding: University of Glasgow

Nature Communications, 2023, vol. 14, issue 1, 1-19

Abstract: Abstract Iron is essential to cells as a cofactor in enzymes of respiration and replication, however without correct storage, iron leads to the formation of dangerous oxygen radicals. In yeast and plants, iron is transported into a membrane-bound vacuole by the vacuolar iron transporter (VIT). This transporter is conserved in the apicomplexan family of obligate intracellular parasites, including in Toxoplasma gondii. Here, we assess the role of VIT and iron storage in T. gondii. By deleting VIT, we find a slight growth defect in vitro, and iron hypersensitivity, confirming its essential role in parasite iron detoxification, which can be rescued by scavenging of oxygen radicals. We show VIT expression is regulated by iron at transcript and protein levels, and by altering VIT localization. In the absence of VIT, T. gondii responds by altering expression of iron metabolism genes and by increasing antioxidant protein catalase activity. We also show that iron detoxification has an important role both in parasite survival within macrophages and in virulence in a mouse model. Together, by demonstrating a critical role for VIT during iron detoxification in T. gondii, we reveal the importance of iron storage in the parasite and provide the first insight into the machinery involved.

Date: 2023
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DOI: 10.1038/s41467-023-39436-y

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