Document Detail


BID is cleaved by caspase-8 within a native complex on the mitochondrial membrane.
MedLine Citation:
PMID:  21072056     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Z T Schug; F Gonzalvez; R H Houtkooper; F M Vaz; E Gottlieb
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-11-12
Journal Detail:
Title:  Cell death and differentiation     Volume:  18     ISSN:  1476-5403     ISO Abbreviation:  Cell Death Differ.     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-02-14     Completed Date:  2011-05-31     Revised Date:  2012-03-01    
Medline Journal Info:
Nlm Unique ID:  9437445     Medline TA:  Cell Death Differ     Country:  England    
Other Details:
Languages:  eng     Pagination:  538-48     Citation Subset:  IM    
Affiliation:
Laboratory of Apoptosis and Tumour Metabolism, Cancer Research UK, The Beatson Institute for Cancer Research, Glasgow G61 1BD, UK.
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MeSH Terms
Descriptor/Qualifier:
Antigens, CD95 / 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:
//Cancer Research UK
Chemical
Reg. No./Substance:
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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