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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
2007-5-18
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pubmed:abstractText |
Most cell death stimuli trigger the mitochondrial release of cytochrome c and other cofactors that induce caspase activation and ensuing apoptosis. Apoptosis is also associated with massive mitochondrial fragmentation and cristae remodeling. Dynamin-related protein 1 (Drp1), a protein of the mitochondrial fission machinery, has been reported to participate in apoptotic mitochondrial fragmentation. Several theories explaining the mechanisms of cytochrome c release have been proposed. One suggests that it relies on the activation of Drp1-mediated mitochondrial fission. Here, we report that downregulation of Drp1 inhibits fragmentation of the mitochondrial network and partially prevents the release of cytochrome c but fails to prevent the release of other mitochondrial factors such as second mitochondria-derived activator of caspase/direct IAP-binding protein with low pI, Omi/HtrA2, adenylate kinase 2 and deafness dystonia peptide/TIMM8a. An explanation for the prevention of cytochrome c release is provided by our observation that inhibiting Drp1-mediated mitochondrial fission prevents the mitochondrial release of soluble OPA1 that was proposed to regulate cristae remodeling and complete cytochrome c release during apoptosis. Finally, we observed that downregulation of Drp1 delays but does not inhibit apoptosis, suggesting that mitochondrial fragmentation is not a prerequisite for apoptosis.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adenylate Kinase,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochromes c,
http://linkedlifedata.com/resource/pubmed/chemical/DNM1L protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/GTP Phosphohydrolases,
http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Transport Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Microtubule-Associated Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Mitochondrial Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/OPA1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Omi serine protease,
http://linkedlifedata.com/resource/pubmed/chemical/Serine Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/TIMM8A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/adenylate kinase 2
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1350-9047
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
14
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1086-94
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pubmed:dateRevised |
2009-9-4
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pubmed:meshHeading |
pubmed-meshheading:17332775-Adenylate Kinase,
pubmed-meshheading:17332775-Apoptosis,
pubmed-meshheading:17332775-Caspases,
pubmed-meshheading:17332775-Cytochromes c,
pubmed-meshheading:17332775-Flow Cytometry,
pubmed-meshheading:17332775-GTP Phosphohydrolases,
pubmed-meshheading:17332775-HeLa Cells,
pubmed-meshheading:17332775-Humans,
pubmed-meshheading:17332775-Immunoblotting,
pubmed-meshheading:17332775-Isoenzymes,
pubmed-meshheading:17332775-Membrane Transport Proteins,
pubmed-meshheading:17332775-Microscopy, Fluorescence,
pubmed-meshheading:17332775-Microtubule-Associated Proteins,
pubmed-meshheading:17332775-Mitochondria,
pubmed-meshheading:17332775-Mitochondrial Proteins,
pubmed-meshheading:17332775-RNA Interference,
pubmed-meshheading:17332775-Serine Endopeptidases
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pubmed:year |
2007
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pubmed:articleTitle |
Inhibiting Drp1-mediated mitochondrial fission selectively prevents the release of cytochrome c during apoptosis.
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pubmed:affiliation |
Unité de Physiopathologie des Infections Lentivirales, Institut Pasteur, 28 rue du Dr. Roux, 75724 Paris cedex 15, France.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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