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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2006-3-6
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pubmed:abstractText |
Iron-sulfur (Fe-S) clusters are required for the functions of mitochondrial aconitase, mammalian iron regulatory protein 1, and many other proteins in multiple subcellular compartments. Recent studies in Saccharomyces cerevisiae indicated that Fe-S cluster biogenesis also has an important role in mitochondrial iron homeostasis. Here we report the functional analysis of the mitochondrial and cytosolic isoforms of the human Fe-S cluster scaffold protein, ISCU. Suppression of human ISCU by RNAi not only inactivated mitochondrial and cytosolic aconitases in a compartment-specific manner but also inappropriately activated the iron regulatory proteins and disrupted intracellular iron homeostasis. Furthermore, endogenous ISCU levels were suppressed by iron deprivation. These results provide evidence for a coordinated response to iron deficiency that includes activation of iron uptake, redistribution of intracellular iron, and decreased utilization of iron in Fe-S proteins.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
1550-4131
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
3
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
199-210
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pubmed:dateRevised |
2007-7-25
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pubmed:meshHeading |
pubmed-meshheading:16517407-Aconitate Hydratase,
pubmed-meshheading:16517407-Cells, Cultured,
pubmed-meshheading:16517407-Cytosol,
pubmed-meshheading:16517407-Gene Expression Regulation,
pubmed-meshheading:16517407-Gene Silencing,
pubmed-meshheading:16517407-HeLa Cells,
pubmed-meshheading:16517407-Homeostasis,
pubmed-meshheading:16517407-Humans,
pubmed-meshheading:16517407-Iron,
pubmed-meshheading:16517407-Iron Regulatory Protein 1,
pubmed-meshheading:16517407-Iron Regulatory Protein 2,
pubmed-meshheading:16517407-Iron-Sulfur Proteins,
pubmed-meshheading:16517407-Mitochondria,
pubmed-meshheading:16517407-Models, Biological,
pubmed-meshheading:16517407-Protein Binding,
pubmed-meshheading:16517407-Protein Isoforms,
pubmed-meshheading:16517407-RNA, Small Interfering,
pubmed-meshheading:16517407-Response Elements
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pubmed:year |
2006
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pubmed:articleTitle |
Functions of mitochondrial ISCU and cytosolic ISCU in mammalian iron-sulfur cluster biogenesis and iron homeostasis.
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pubmed:affiliation |
National Institute of Child Health and Human Development, Cell Biology and Metabolism Branch, Bethesda, Maryland 20892, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Intramural
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