The vacuolar iron transporter mediates iron detoxification in Toxoplasma gondii

Aghabi, D., Sloan, M. , Gill, G., Hartmann, E., Antipova, O., Dou, Z., Guerra, A. J., Carruthers, V. B. and Harding, C. R. (2023) The vacuolar iron transporter mediates iron detoxification in Toxoplasma gondii. Nature Communications, 14, 3659. (doi: 10.1038/s41467-023-39436-y) (PMID:37339985) (PMCID:PMC10281983)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Gill, Grace and Harding, Dr Clare and Sloan, Dr Megan and Aghabi, Dana and Hartmann, Miss Elena
• Authors: Aghabi, D., Sloan, M., Gill, G., Hartmann, E., Antipova, O., Dou, Z., Guerra, A. J., Carruthers, V. B., and Harding, C. R.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Nature Communications
• Publisher: Nature Research
• ISSN: 2041-1723
• ISSN (Online): 2041-1723
• Copyright Holders: Copyright © 2023 The Authors
• First Published: First published in Nature Communications 14:3659
• Publisher Policy: Reproduced under a Creative Commons licence

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
304336		Iron usage in the eukaryotic parasite Toxoplasma gondii	Clare Harding	Wellcome Trust (WELLCOTR)	213455/Z/18/Z	III - Parasitology