Document Detail


Cyclophilin D-dependent mitochondrial permeability transition regulates some necrotic but not apoptotic cell death.
MedLine Citation:
PMID:  15800626     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Mitochondria play an important role in energy production, Ca2+ homeostasis and cell death. In recent years, the role of the mitochondria in apoptotic and necrotic cell death has attracted much attention. In apoptosis and necrosis, the mitochondrial permeability transition (mPT), which leads to disruption of the mitochondrial membranes and mitochondrial dysfunction, is considered to be one of the key events, although its exact role in cell death remains elusive. We therefore created mice lacking cyclophilin D (CypD), a protein considered to be involved in the mPT, to analyse its role in cell death. CypD-deficient mice were developmentally normal and showed no apparent anomalies, but CypD-deficient mitochondria did not undergo the cyclosporin A-sensitive mPT. CypD-deficient cells died normally in response to various apoptotic stimuli, but showed resistance to necrotic cell death induced by reactive oxygen species and Ca2+ overload. In addition, CypD-deficient mice showed a high level of resistance to ischaemia/reperfusion-induced cardiac injury. Our results indicate that the CypD-dependent mPT regulates some forms of necrotic death, but not apoptotic death.
Authors:
Takashi Nakagawa; Shigeomi Shimizu; Tetsuya Watanabe; Osamu Yamaguchi; Kinya Otsu; Hirotaka Yamagata; Hidenori Inohara; Takeshi Kubo; Yoshihide Tsujimoto
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Nature     Volume:  434     ISSN:  1476-4687     ISO Abbreviation:  Nature     Publication Date:  2005 Mar 
Date Detail:
Created Date:  2005-03-31     Completed Date:  2005-04-08     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0410462     Medline TA:  Nature     Country:  England    
Other Details:
Languages:  eng     Pagination:  652-8     Citation Subset:  IM    
Affiliation:
Laboratory of Molecular Genetics, Department of Post-Genomics and Diseases, Japan Science and Technology Corporation, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / drug effects
Calcium / metabolism,  pharmacology
Caspases / metabolism
Cells, Cultured
Cyclophilins / deficiency,  genetics,  metabolism*
Enzyme Activation / drug effects
Fibroblasts / cytology,  pathology
Hepatocytes / cytology,  drug effects,  metabolism,  pathology
Hydrogen Peroxide / pharmacology
Mice
Mice, Knockout
Mitochondria, Liver / genetics,  metabolism*,  pathology
Mitochondrial Swelling / physiology
Myocardial Ischemia / genetics,  metabolism,  pathology
Myocardial Reperfusion Injury / genetics,  metabolism,  pathology
Necrosis*
Reactive Oxygen Species / metabolism,  pharmacology
Thymus Gland / cytology,  pathology
Chemical
Reg. No./Substance:
0/Reactive Oxygen Species; 7440-70-2/Calcium; 7722-84-1/Hydrogen Peroxide; EC 3.4.22.-/Caspases; EC 5.2.1.-/Cyclophilins; EC 5.2.1.8/cyclophilin D
Comments/Corrections
Comment In:
Nature. 2005 Mar 31;434(7033):578-9   [PMID:  15800609 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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