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

Soltani, Sattar; Webb, Samuel M.; Kroll, Thomas; King-Jones, Kirst

doi:10.1038/s41467-024-48165-9

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

Journal Article · 14 May 2024 · Nature Communications

DOI: https://doi.org/10.1038/s41467-024-48165-9 · OSTI ID:2350749

Soltani, Sattar; Webb, Samuel M.; Kroll, Thomas;

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.

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Sponsoring Organization:: USDOE

Grant/Contract Number:: NONE; AC02-76SF00515

OSTI ID:: 2350749

Journal Information:: Nature Communications, Journal Name: Nature Communications Journal Issue: 1 Vol. 15; ISSN 2041-1723

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United Kingdom

Language:: English

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