| Genetic analysis of iron citrate toxicity in yeast: implications for mammalian iron homeostasis. | |
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MedLine Citation:
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PMID: 12471153 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Deletion of the yeast homologue of frataxin, YFH1, results in mitochondrial iron accumulation and respiratory deficiency (petite formation). We used a genetic screen to identify mutants that modify iron-associated defects in respiratory activity in Deltayfh1 cells. A deletion in the peroxisomal citrate synthase CIT2 in Deltayfh1 cells decreased the rate of petite formation. Conversely, overexpression of CIT2 in Deltayfh1 cells increased the rate of respiratory loss. Citrate toxicity in Deltayfh1 cells was dependent on iron but was independent of mitochondrial respiration. Citrate toxicity was not restricted to iron-laden mitochondria but also occurred when iron accumulated in cytosol because of impaired vacuolar iron storage. These results suggest that high levels of citrate may promote iron-mediated tissue damage. |
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Authors:
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Opal S Chen; Shawn Hemenway; Jerry Kaplan |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. Date: 2002-12-06 |
Journal Detail:
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Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 99 ISSN: 0027-8424 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 2002 Dec |
Date Detail:
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Created Date: 2002-12-24 Completed Date: 2003-01-21 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
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Languages: eng Pagination: 16922-7 Citation Subset: IM |
Affiliation:
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Department of Pathology, School of Medicine, University of Utah, Salt Lake City, UT 84132, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Citrate (si)-Synthase
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physiology Citric Acid / toxicity* Fungal Proteins / physiology Homeostasis Intracellular Signaling Peptides and Proteins Iron / metabolism*, toxicity* Mitochondria / drug effects Oxygen Consumption Saccharomyces cerevisiae / drug effects*, genetics, metabolism Saccharomyces cerevisiae Proteins* |
| Grant Support | |
ID/Acronym/Agency:
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CA42014/CA/NCI NIH HHS; DK-52380/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Fungal Proteins; 0/Intracellular Signaling Peptides and Proteins; 0/RTG2 protein, S cerevisiae; 0/Saccharomyces cerevisiae Proteins; 7439-89-6/Iron; 77-92-9/Citric Acid; EC 2.3.3.1/Citrate (si)-Synthase |
| Comments/Corrections | |
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