Document Detail


Genetic analysis of iron citrate toxicity in yeast: implications for mammalian iron homeostasis.
MedLine Citation:
PMID:  12471153     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Opal S Chen; Shawn Hemenway; Jerry Kaplan
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.     Date:  2002-12-06
Journal Detail:
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:
Created Date:  2002-12-24     Completed Date:  2003-01-21     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  16922-7     Citation Subset:  IM    
Affiliation:
Department of Pathology, School of Medicine, University of Utah, Salt Lake City, UT 84132, USA.
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MeSH Terms
Descriptor/Qualifier:
Citrate (si)-Synthase / 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:
CA42014/CA/NCI NIH HHS; DK-52380/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
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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