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dc.contributor.authorJeong, Suh Young
dc.contributor.authorCrooks, Daniel R.
dc.contributor.authorWilson-Ollivierre, Hayden
dc.contributor.authorGhosh, Manik C.
dc.contributor.authorSougrat, Rachid
dc.contributor.authorLee, Jaekwon
dc.contributor.authorCooperman, Sharon
dc.contributor.authorMitchell, James B.
dc.contributor.authorBeaumont, Carole
dc.contributor.authorRouault, Tracey A.
dc.date.accessioned2014-08-27T09:45:27Z
dc.date.available2014-08-27T09:45:27Z
dc.date.issued2011-10-07
dc.identifier.citationJeong SY, Crooks DR, Wilson-Ollivierre H, Ghosh MC, Sougrat R, et al. (2011) Iron Insufficiency Compromises Motor Neurons and Their Mitochondrial Function in Irp2-Null Mice. PLoS ONE 6: e25404. doi:10.1371/journal.pone.0025404.
dc.identifier.issn19326203
dc.identifier.pmid22003390
dc.identifier.doi10.1371/journal.pone.0025404
dc.identifier.urihttp://hdl.handle.net/10754/325294
dc.description.abstractGenetic ablation of Iron Regulatory Protein 2 (Irp2, Ireb2), which post-transcriptionally regulates iron metabolism genes, causes a gait disorder in mice that progresses to hind-limb paralysis. Here we have demonstrated that misregulation of iron metabolism from loss of Irp2 causes lower motor neuronal degeneration with significant spinal cord axonopathy. Mitochondria in the lumbar spinal cord showed significantly decreased Complex I and II activities, and abnormal morphology. Lower motor neurons appeared to be the most adversely affected neurons, and we show that functional iron starvation due to misregulation of iron import and storage proteins, including transferrin receptor 1 and ferritin, may have a causal role in disease. We demonstrated that two therapeutic approaches were beneficial for motor neuron survival. First, we activated a homologous protein, IRP1, by oral Tempol treatment and found that axons were partially spared from degeneration. Secondly, we genetically decreased expression of the iron storage protein, ferritin, to diminish functional iron starvation. These data suggest that functional iron deficiency may constitute a previously unrecognized molecular basis for degeneration of motor neurons in mice.
dc.language.isoen
dc.publisherPublic Library of Science (PLoS)
dc.rightsThis is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
dc.rightsArchived with thanks to PLoS ONE
dc.subjectCD71 antigen
dc.subjectferritin
dc.subjectiron
dc.subjectiron regulatory protein 1
dc.subjectiron regulatory protein 2
dc.subjectreduced nicotinamide adenine dinucleotide dehydrogenase (ubiquinone)
dc.subjectsuccinate dehydrogenase (ubiquinone)
dc.subjectamine oxide
dc.subjectapoferritin
dc.subjectbiological marker
dc.subjectiron
dc.subjectiron regulatory protein 1
dc.subjectiron regulatory protein 2
dc.subjecttempol
dc.subjectanimal experiment
dc.subjectanimal tissue
dc.subjectcell function
dc.subjectcell lysate
dc.subjectcontrolled study
dc.subjectDNA modification
dc.subjectenzyme activity
dc.subjectgene expression regulation
dc.subjecthomeostasis
dc.subjectimmunohistochemistry
dc.subjectiron deficiency
dc.subjectiron storage
dc.subjectlumbar spinal cord
dc.subjectmitochondrion
dc.subjectmotoneuron
dc.subjectmouse
dc.subjectnerve cell degeneration
dc.subjectnerve fiber degeneration
dc.subjectneuropathy
dc.subjectprotein synthesis
dc.subjectatrophy
dc.subjectbiosynthesis
dc.subjectbrain
dc.subjectdrug effect
dc.subjectgene deletion
dc.subjectgenetics
dc.subjectmetabolism
dc.subjectmitochondrion
dc.subjectnerve fiber
dc.subjectoxidative stress
dc.subjectpathology
dc.subjectspin labeling
dc.subjectspinal cord
dc.subjectMus
dc.subjectApoferritins
dc.subjectAtrophy
dc.subjectAxons
dc.subjectBiological Markers
dc.subjectBrain
dc.subjectCyclic N-Oxides
dc.subjectGene Deletion
dc.subjectHomeostasis
dc.subjectIron
dc.subjectIron Regulatory Protein 1
dc.subjectIron Regulatory Protein 2
dc.subjectMice
dc.subjectMitochondria
dc.subjectMotor Neurons
dc.subjectOxidative Stress
dc.subjectSpin Labels
dc.subjectSpinal Cord
dc.titleIron insufficiency compromises motor neurons and their mitochondrial function in Irp2-null mice
dc.typeArticle
dc.contributor.departmentImaging and Characterization Core Lab
dc.identifier.journalPLoS ONE
dc.identifier.pmcidPMC3189198
dc.eprint.versionPublisher's Version/PDF
dc.contributor.institutionEunice Kennedy Shriver National Institute of Child Health and Development, National Institutes of Health, Bethesda, MD, United States
dc.contributor.institutionDepartment of Biochemistry, University of Nebraska, Lincoln, NE, United States
dc.contributor.institutionNational Cancer Institute, National Institutes of Health, Bethesda, MD, United States
dc.contributor.institutionINSERM U773, Centre de Recherche Biomdicale Bichat-Beaujon, Universit Paris Diderot, Paris, France
dc.contributor.affiliationKing Abdullah University of Science and Technology (KAUST)
kaust.personSougrat, Rachid
refterms.dateFOA2018-06-13T14:50:15Z


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