| Cyclophilin D-dependent mitochondrial permeability transition regulates some necrotic but not apoptotic cell death. | |
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MedLine Citation:
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PMID: 15800626 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Takashi Nakagawa; Shigeomi Shimizu; Tetsuya Watanabe; Osamu Yamaguchi; Kinya Otsu; Hirotaka Yamagata; Hidenori Inohara; Takeshi Kubo; Yoshihide Tsujimoto |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Nature Volume: 434 ISSN: 1476-4687 ISO Abbreviation: Nature Publication Date: 2005 Mar |
Date Detail:
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Created Date: 2005-03-31 Completed Date: 2005-04-08 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0410462 Medline TA: Nature Country: England |
Other Details:
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Languages: eng Pagination: 652-8 Citation Subset: IM |
Affiliation:
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Laboratory of Molecular Genetics, Department of Post-Genomics and Diseases, Japan Science and Technology Corporation, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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:
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Nature. 2005 Mar 31;434(7033):578-9
[PMID:
15800609
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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