Document Detail

Lysosomal proteolysis is the primary degradation pathway for cytosolic ferritin and cytosolic ferritin degradation is necessary for iron exit.
MedLine Citation:
PMID:  20406137     Owner:  NLM     Status:  MEDLINE    
Cytosolic ferritins sequester and store iron, consequently protecting cells against iron-mediated free radical damage. However, the mechanisms of iron exit from the ferritin cage and reutilization are largely unknown. In a previous study, we found that mitochondrial ferritin (MtFt) expression led to a decrease in cytosolic ferritin. Here we showed that treatment with inhibitors of lysosomal proteases largely blocked cytosolic ferritin loss in both MtFt-expressing and wild-type cells. Moreover, cytosolic ferritin in cells treated with inhibitors of lysosomal proteases was found to store more iron than did cytosolic ferritins in untreated cells. The prevention of cytosolic ferritin degradation in MtFt-expressing cells significantly blocked iron mobilization from the protein cage induced by MtFt expression. These studies also showed that blockage of cytosolic ferritin loss by leupeptin resulted in decreased cytosolic ferritin synthesis and prolonged cytosolic ferritin stability, potentially resulting in diminished iron availability. Lastly, we found that proteasomes were responsible for cytosolic ferritin degradation in cells pretreated with ferric ammonium citrate. Thus, the current studies suggest that cytosolic ferritin degradation precedes the release of iron in MtFt-expressing cells; that MtFt-induced cytosolic ferritin decrease is partially preventable by lysosomal protease inhibitors; and that both lysosomal and proteasomal pathways may be involved in cytosolic ferritin degradation.
Yinghui Zhang; Marc Mikhael; Dongxue Xu; Yiye Li; Shan Soe-Lin; Bo Ning; Wei Li; Guangjun Nie; Yuliang Zhao; Prem Ponka
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Antioxidants & redox signaling     Volume:  13     ISSN:  1557-7716     ISO Abbreviation:  Antioxid. Redox Signal.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-08-20     Completed Date:  2011-01-24     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100888899     Medline TA:  Antioxid Redox Signal     Country:  United States    
Other Details:
Languages:  eng     Pagination:  999-1009     Citation Subset:  IM    
CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China, Beijing, China.
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MeSH Terms
Cell Line
Cytosol / metabolism*
Ferric Compounds / pharmacology
Ferritins / metabolism*
Iron / metabolism*
Leupeptins / pharmacology
Lysosomes / metabolism*
Mitochondria / metabolism
Peptide Hydrolases / metabolism*
Protease Inhibitors / pharmacology
Proteasome Endopeptidase Complex / metabolism
Quaternary Ammonium Compounds / pharmacology
Grant Support
//Canadian Institutes of Health Research
Reg. No./Substance:
0/Ferric Compounds; 0/Leupeptins; 0/Protease Inhibitors; 0/Quaternary Ammonium Compounds; 1185-57-5/ferric ammonium citrate; 24365-47-7/leupeptin; 7439-89-6/Iron; 9007-73-2/Ferritins; EC 3.4.-/Peptide Hydrolases; EC Endopeptidase Complex

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