Document Detail


Apoptosome-deficient cells lose cytochrome c through proteasomal degradation but survive by autophagy-dependent glycolysis.
MedLine Citation:
PMID:  18550800     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cytochrome c release from mitochondria promotes apoptosome formation and caspase activation. The question as to whether mitochondrial permeabilization kills cells via a caspase-independent pathway when caspase activation is prevented is still open. Here we report that proneural cells of embryonic origin, when induced to die but rescued by apoptosome inactivation are deprived of cytosolic cytochrome c through proteasomal degradation. We also show that, in this context, those cells keep generating ATP by glycolysis for a long period of time and that they keep their mitochondria in a depolarized state that can be reverted. Moreover, under these conditions, such apoptosome-deficient cells activate a Beclin 1-dependent autophagy pathway to sustain glycolytic-dependent ATP production. Our findings contribute to elucidating what the point-of-no-return in apoptosis is. They also help in clarifying the issue of survival of apoptosome-deficient proneural cells under stress conditions. Unraveling this issue could be highly relevant for pharmacological intervention and for therapies based on neural stem cell transfer in the treatment of neurological disorders.
Authors:
Elisabetta Ferraro; Angela Pulicati; Maria Teresa Cencioni; Mauro Cozzolino; Francesca Navoni; Simona di Martino; Roberta Nardacci; Maria Teresa Carrì; Francesco Cecconi
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-06-11
Journal Detail:
Title:  Molecular biology of the cell     Volume:  19     ISSN:  1939-4586     ISO Abbreviation:  Mol. Biol. Cell     Publication Date:  2008 Aug 
Date Detail:
Created Date:  2008-07-29     Completed Date:  2008-12-22     Revised Date:  2011-11-24    
Medline Journal Info:
Nlm Unique ID:  9201390     Medline TA:  Mol Biol Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3576-88     Citation Subset:  IM    
Affiliation:
Laboratory of Molecular Neuroembryology, IRCCS Fondazione Santa Lucia, 00143, Rome, Italy.
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MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphate / metabolism
Animals
Apoptosis*
Apoptosis Regulatory Proteins
Apoptosomes / metabolism*
Autophagy*
Caspases / metabolism
Cell Survival
Cytochromes c / metabolism*
Enzyme Activation
Gene Expression Regulation*
Glycolysis
Mice
Models, Biological
Proteasome Endopeptidase Complex / metabolism*
Proteins / metabolism
Grant Support
ID/Acronym/Agency:
TCR04004//Telethon
Chemical
Reg. No./Substance:
0/Apoptosis Regulatory Proteins; 0/Apoptosomes; 0/Becn1 protein, mouse; 0/Proteins; 56-65-5/Adenosine Triphosphate; 9007-43-6/Cytochromes c; EC 3.4.22.-/Caspases; EC 3.4.25.1/Proteasome Endopeptidase Complex
Comments/Corrections

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


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