New molecular components of high and low affinity iron import systems in Drosophila

Abstract The high abundance and molecular versatility of iron have led to its universal presence in biological systems, yet its absorption is exceptionally challenging. Animals and yeasts use divalent metal transporters to import iron, but yeasts also employ the multicopper oxidase Fet3p for high-af...

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Main Authors: Sattar Soltani, Minyi Yan, Qingxuan Yu, Areeg Abd Elhafiz, Erika Pfriem, Samuel M. Webb, Thomas Kroll, Jahir Marceliano Bahena Lopez, Fanis Missirlis, Kirst King-Jones
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-60758-6
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author Sattar Soltani
Minyi Yan
Qingxuan Yu
Areeg Abd Elhafiz
Erika Pfriem
Samuel M. Webb
Thomas Kroll
Jahir Marceliano Bahena Lopez
Fanis Missirlis
Kirst King-Jones
author_facet Sattar Soltani
Minyi Yan
Qingxuan Yu
Areeg Abd Elhafiz
Erika Pfriem
Samuel M. Webb
Thomas Kroll
Jahir Marceliano Bahena Lopez
Fanis Missirlis
Kirst King-Jones
author_sort Sattar Soltani
collection DOAJ
description Abstract The high abundance and molecular versatility of iron have led to its universal presence in biological systems, yet its absorption is exceptionally challenging. Animals and yeasts use divalent metal transporters to import iron, but yeasts also employ the multicopper oxidase Fet3p for high-affinity iron uptake when iron-starved. Using long-term iron depletion in Drosophila, we identified four components involved in iron absorption: Multicopper oxidase-4 (Mco4), a Fet3p ortholog, is essential for surviving iron starvation, whereas the cytochrome b561 enzymes Fire (Ferric Iron Reductase) and Fire-like, as well as cytochrome b5 protein Firewood, are required for iron absorption under normal conditions. This study reports the presence of a high-affinity iron uptake system in an animal, a cytochrome b5 electron donor for ferric iron reduction, and intestinal ferric reductases, and provides a valuable resource for further exploration of genes involved in iron homeostasis, transport, and absorption.
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spelling doaj-art-2e5bd6d36f5740b09c51fd0137ca4f092025-08-20T03:03:44ZengNature PortfolioNature Communications2041-17232025-07-0116112210.1038/s41467-025-60758-6New molecular components of high and low affinity iron import systems in DrosophilaSattar Soltani0Minyi Yan1Qingxuan Yu2Areeg Abd Elhafiz3Erika Pfriem4Samuel M. Webb5Thomas Kroll6Jahir Marceliano Bahena Lopez7Fanis Missirlis8Kirst King-Jones9Department of Biological Sciences, University of AlbertaDepartment of Biological Sciences, University of AlbertaDepartment of Biological Sciences, University of AlbertaDepartment of Biological Sciences, University of AlbertaDepartment of Biological Sciences, University of AlbertaStanford Synchrotron Radiation Lightsource, SLAC National Accelerator LaboratoryStanford Synchrotron Radiation Lightsource, SLAC National Accelerator LaboratoryDepartamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados (Cinvestav)Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados (Cinvestav)Department of Biological Sciences, University of AlbertaAbstract The high abundance and molecular versatility of iron have led to its universal presence in biological systems, yet its absorption is exceptionally challenging. Animals and yeasts use divalent metal transporters to import iron, but yeasts also employ the multicopper oxidase Fet3p for high-affinity iron uptake when iron-starved. Using long-term iron depletion in Drosophila, we identified four components involved in iron absorption: Multicopper oxidase-4 (Mco4), a Fet3p ortholog, is essential for surviving iron starvation, whereas the cytochrome b561 enzymes Fire (Ferric Iron Reductase) and Fire-like, as well as cytochrome b5 protein Firewood, are required for iron absorption under normal conditions. This study reports the presence of a high-affinity iron uptake system in an animal, a cytochrome b5 electron donor for ferric iron reduction, and intestinal ferric reductases, and provides a valuable resource for further exploration of genes involved in iron homeostasis, transport, and absorption.https://doi.org/10.1038/s41467-025-60758-6
spellingShingle Sattar Soltani
Minyi Yan
Qingxuan Yu
Areeg Abd Elhafiz
Erika Pfriem
Samuel M. Webb
Thomas Kroll
Jahir Marceliano Bahena Lopez
Fanis Missirlis
Kirst King-Jones
New molecular components of high and low affinity iron import systems in Drosophila
Nature Communications
title New molecular components of high and low affinity iron import systems in Drosophila
title_full New molecular components of high and low affinity iron import systems in Drosophila
title_fullStr New molecular components of high and low affinity iron import systems in Drosophila
title_full_unstemmed New molecular components of high and low affinity iron import systems in Drosophila
title_short New molecular components of high and low affinity iron import systems in Drosophila
title_sort new molecular components of high and low affinity iron import systems in drosophila
url https://doi.org/10.1038/s41467-025-60758-6
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