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Drosophila Evi5 is a critical regulator of intracellular iron transport via transferrin and ferritin interactions

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  • Sattar Soltani

    (University of Alberta, Faculty of Science)

  • Samuel M. Webb

    (Stanford Synchrotron Radiation Lightsource SLAC National Accelerator Laboratory)

  • Thomas Kroll

    (Stanford Synchrotron Radiation Lightsource SLAC National Accelerator Laboratory)

  • Kirst King-Jones

    (University of Alberta, Faculty of Science)

Abstract

Vesicular transport is essential for delivering cargo to intracellular destinations. Evi5 is a Rab11-GTPase-activating protein involved in endosome recycling. In humans, Evi5 is a high-risk locus for multiple sclerosis, a debilitating disease that also presents with excess iron in the CNS. In insects, the prothoracic gland (PG) requires entry of extracellular iron to synthesize steroidogenic enzyme cofactors. The mechanism of peripheral iron uptake in insect cells remains controversial. We show that Evi5-depletion in the Drosophila PG affected vesicle morphology and density, blocked endosome recycling and impaired trafficking of transferrin-1, thus disrupting heme synthesis due to reduced cellular iron concentrations. We show that ferritin delivers iron to the PG as well, and interacts physically with Evi5. Further, ferritin-injection rescued developmental delays associated with Evi5-depletion. To summarize, our findings show that Evi5 is critical for intracellular iron trafficking via transferrin-1 and ferritin, and implicate altered iron homeostasis in the etiology of multiple sclerosis.

Suggested Citation

  • Sattar Soltani & Samuel M. Webb & Thomas Kroll & Kirst King-Jones, 2024. "Drosophila Evi5 is a critical regulator of intracellular iron transport via transferrin and ferritin interactions," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48165-9
    DOI: 10.1038/s41467-024-48165-9
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    References listed on IDEAS

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    1. Roland Lill, 2009. "Function and biogenesis of iron–sulphur proteins," Nature, Nature, vol. 460(7257), pages 831-838, August.
    2. Nhan Huynh & Qiuxiang Ou & Pendleton Cox & Roland Lill & Kirst King-Jones, 2019. "Glycogen branching enzyme controls cellular iron homeostasis via Iron Regulatory Protein 1 and mitoNEET," Nature Communications, Nature, vol. 10(1), pages 1-18, December.
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