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Huynh, N., Ou, Q., Cox, P., Lill, R., King-Jones, K. (2019). Glycogen branching enzyme controls cellular iron homeostasis via Iron Regulatory Protein 1 and mitoNEET.  Nat. Commun. 10(1): 5463.
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Research paper

Iron Regulatory Protein 1 (IRP1) is a bifunctional cytosolic iron sensor. When iron levels are normal, IRP1 harbours an iron-sulphur cluster (holo-IRP1), an enzyme with aconitase activity. When iron levels fall, IRP1 loses the cluster (apo-IRP1) and binds to iron-responsive elements (IREs) in messenger RNAs (mRNAs) encoding proteins involved in cellular iron uptake, distribution, and storage. Here we show that mutations in the Drosophila 1,4-Alpha-Glucan Branching Enzyme (AGBE) gene cause porphyria. AGBE was hitherto only linked to glycogen metabolism and a fatal human disorder known as glycogen storage disease type IV. AGBE binds specifically to holo-IRP1 and to mitoNEET, a protein capable of repairing IRP1 iron-sulphur clusters. This interaction ensures nuclear translocation of holo-IRP1 and downregulation of iron-dependent processes, demonstrating that holo-IRP1 functions not just as an aconitase, but throttles target gene expression in anticipation of declining iron requirements.

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PubMed Central ID
PMC6884552 (PMC) (EuropePMC)
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Personal communication to FlyBase

Location data for Irp-1A[KO] and Irp-1B[KO] deletions.
Huynh and King-Jones, 2020.8.14, Location data for Irp-1A[KO] and Irp-1B[KO] deletions. [FBrf0246450]

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    Nature communications
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