Abstract
In low-iron conditions, the cytosolic iron-regulatory protein IRP1 binds to iron-responsive elements (IREs) in mRNAs encoding iron-regulated proteins. In high-iron conditions, IRP1 incorporates an iron-sulfur cluster (ISC), which interferes with IRE binding and prevents intracellular iron accumulation. Here we demonstrate an incomplete shift of IRP1 to its ISC form in Friedreich ataxia (FRDA) fibroblasts, associated with decreased activities of ISC respiratory complexes. Our data suggest an impaired adaptive response to iron accumulation in FRDA cells.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Cells, Cultured
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Dose-Response Relationship, Drug
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Electron Transport Complex I / metabolism
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Electron Transport Complex II / metabolism
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Electrophoretic Mobility Shift Assay / methods
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Fibroblasts / metabolism
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Friedreich Ataxia / metabolism*
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Friedreich Ataxia / pathology
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Humans
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Iron / pharmacology
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Iron Regulatory Protein 1 / metabolism*
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Iron-Regulatory Proteins / metabolism
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Protein Binding / drug effects
Substances
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Iron-Regulatory Proteins
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Iron
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Electron Transport Complex II
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Iron Regulatory Protein 1
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Electron Transport Complex I