Abstract

Iron is essential to living cells, acting as a cofactor in a number of essential enzymes in metabolism; however, proper storage of iron is required or it can be dangerous to the cell. In both yeast and plants, iron is stored in a vacuole through the action of a vacuolar iron transporter (VIT). This transporter is conserved in the apicomplexan family of obligate intracellular parasites, including in Toxoplasma gondii, a pathogen of medical and veterinary importance. I will discuss the role of VIT in T. gondii. We show that deletion of VIT causes a slight growth defect in vitro, however leads to hypersensitivity in the presence of excess iron, confirming its essential role in iron detoxification in the parasite. In the absence of VIT , parasites contain less iron and are at a growth disadvantage when moving into an iron-depleted environment. We show parasite VIT expression is regulated by environmental iron levels at both the transcript and protein level, and by altering the distribution of VIT within the cell. In the absence of VIT , we find that the T. gondii responds by altering expression of genes with a role in iron metabolism. We also show that iron detoxification has an important role both in parasite survival within macrophages and in pathogenesis in a mouse model. We go onto investigate how the parasites respond to altered iron availability within the cell, at both the transcript and protein levels and hypothesize about what this means for metabolic flexibility of these parasites. Together, reveal the importance of iron storage in the parasite and provide the first insight into the machinery involved.

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