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The vacuolar iron transporter mediates iron detoxification in Toxoplasma gondii

Author

Listed:
  • 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
    Cayman Chemical Company)

  • Vern B. Carruthers

    (University of Michigan)

  • Clare R. Harding

    (University of Glasgow)

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.

Suggested Citation

  • Dana Aghabi & Megan Sloan & Grace Gill & Elena Hartmann & Olga Antipova & Zhicheng Dou & Alfredo J. Guerra & Vern B. Carruthers & Clare R. Harding, 2023. "The vacuolar iron transporter mediates iron detoxification in Toxoplasma gondii," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39436-y
    DOI: 10.1038/s41467-023-39436-y
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    References listed on IDEAS

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    1. Yifan Wang & Lamba Omar Sangaré & Tatiana C. Paredes-Santos & Musa A. Hassan & Shruthi Krishnamurthy & Anna M. Furuta & Benedikt M. Markus & Sebastian Lourido & Jeroen P. J. Saeij, 2020. "Genome-wide screens identify Toxoplasma gondii determinants of parasite fitness in IFNγ-activated murine macrophages," Nature Communications, Nature, vol. 11(1), pages 1-19, December.
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