IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-39436-y.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-39436-y
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-023-39436-y?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    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.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.

      More about this item

      Statistics

      Access and download statistics

      Corrections

      All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39436-y. See general information about how to correct material in RePEc.

      If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

      If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

      If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

      For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

      Please note that corrections may take a couple of weeks to filter through the various RePEc services.

      IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.