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Citation
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.
FlyBase ID
FBrf0244135
Publication Type
Research paper
Abstract

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.

PubMed ID
PubMed Central ID
PMC6884552 (PMC) (EuropePMC)
Related Publication(s)
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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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Nat. Commun.
    Title
    Nature communications
    ISBN/ISSN
    2041-1723
    Data From Reference
    Alleles (44)
    Genes (20)
    Human Disease Models (1)
    Physical Interactions (9)
    Cell Lines (1)
    Natural transposons (1)
    Insertions (9)
    Experimental Tools (5)
    Transgenic Constructs (32)