Oxygen-dependent interaction between FBXL5 and CIA targeting complex regulates iron homeostasis
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ABSTRACT: The iron sensing protein FBXL5 is the substrate adaptor for a SKP1-CUL1-RBX1 E3 ubiquitin ligase complex that regulates the degradation of iron regulatory proteins (IRPs). Here we describe a mechanism of FBXL5 regulation involving its interaction with the cytosolic Fe-S cluster assembly (CIA) targeting complex comprised of MMS19, FAM96B, and CIAO1. We demonstrate that the CIA targeting complex promotes the ability of FBXL5 to degrade IRPs. In addition, the FBXL5-CIA targeting complex interaction is regulated by oxygen tension displaying a robust association in 21% O2 that is severely diminished in 1% O2 and contributes to O2-dependent regulation of IRP degradation. Together, these data identify a novel oxygen-dependent signaling axis that links IRP-dependent iron homeostasis with the Fe-S cluster assembly machinery.
INSTRUMENT(S): Orbitrap Fusion Lumos
ORGANISM(S): Homo Sapiens (ncbitaxon:9606)
SUBMITTER: James A. Wohlschlegel
PROVIDER: MSV000083739 | MassIVE | Thu May 02 17:34:00 BST 2019
SECONDARY ACCESSION(S): PXD013697
REPOSITORIES: MassIVE
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