| BID is cleaved by caspase-8 within a native complex on the mitochondrial membrane. | |
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MedLine Citation:
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PMID: 21072056 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Caspase-8 stably inserts into the mitochondrial outer membrane during extrinsic apoptosis. Inhibition of caspase-8 enrichment on the mitochondria impairs caspase-8 activation and prevents apoptosis. However, the function of active caspase-8 on the mitochondrial membrane remains unknown. In this study, we have identified a native complex containing caspase-8 and BID on the mitochondrial membrane, and showed that death receptor activation by Fas or tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induced the cleavage of BID (tBID formation) within this complex. tBID then shifted to separate mitochondria-associated complexes that contained other BCL-2 family members, such as BAK and BCL-X(L). We report that cells stabilize active caspase-8 on the mitochondria in order to specifically target mitochondria-associated BID, and that BID cleavage on the mitochondria is essential for caspase-8-induced cytochrome c release. Our findings indicate that during extrinsic apoptosis, caspase-8 can specifically target BID where it is mostly needed, on the surface of mitochondria. |
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Authors:
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Z T Schug; F Gonzalvez; R H Houtkooper; F M Vaz; E Gottlieb |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-11-12 |
Journal Detail:
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Title: Cell death and differentiation Volume: 18 ISSN: 1476-5403 ISO Abbreviation: Cell Death Differ. Publication Date: 2011 Mar |
Date Detail:
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Created Date: 2011-02-14 Completed Date: 2011-05-31 Revised Date: 2012-03-01 |
Medline Journal Info:
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Nlm Unique ID: 9437445 Medline TA: Cell Death Differ Country: England |
Other Details:
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Languages: eng Pagination: 538-48 Citation Subset: IM |
Affiliation:
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Laboratory of Apoptosis and Tumour Metabolism, Cancer Research UK, The Beatson Institute for Cancer Research, Glasgow G61 1BD, UK. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Antigens, CD95
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metabolism BH3 Interacting Domain Death Agonist Protein / metabolism* Caspase 8 / metabolism* Cell Death / drug effects Cytochromes c / metabolism Green Fluorescent Proteins / metabolism HeLa Cells Humans Membrane Potential, Mitochondrial / drug effects Mitochondria / drug effects, metabolism Mitochondrial Membranes / drug effects, metabolism* Mitochondrial Proteins / metabolism Models, Biological Molecular Weight Mutant Proteins / metabolism Peptide Elongation Factor Tu / metabolism Point Mutation / genetics Protein Binding / drug effects Protein Transport / drug effects Recombinant Proteins / pharmacology TNF-Related Apoptosis-Inducing Ligand / pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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//Cancer Research UK |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD95; 0/BH3 Interacting Domain Death Agonist Protein; 0/FAS protein, human; 0/Mitochondrial Proteins; 0/Mutant Proteins; 0/Recombinant Proteins; 0/TNF-Related Apoptosis-Inducing Ligand; 0/TUFM protein, human; 147336-22-9/Green Fluorescent Proteins; 9007-43-6/Cytochromes c; EC 3.4.22.-/CASP8 protein, human; EC 3.4.22.-/Caspase 8; EC 3.6.1.-/Peptide Elongation Factor Tu |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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