Document Detail


Mitochondrial fission is an upstream and required event for bax foci formation in response to nitric oxide in cortical neurons.
MedLine Citation:
PMID:  17053808     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Mitochondrial dysfunction is an underpinning event in many neurodegenerative disorders. Less clear, however, is how mitochondria become injured during neuronal demise. Nitric oxide (NO) evokes rapid mitochondrial fission in cortical neurons. Interestingly, proapoptotic Bax relocates from the cytoplasm into large foci on mitochondrial scission sites in response to nitrosative stress. Antiapoptotic Bcl-xL does not prevent mitochondrial fission despite its ability to block Bax puncta formation on mitochondria and to mitigate neuronal cell death. Mitofusin 1 (Mfn1) or dominant-negative dynamin-related protein 1(K38A) (Drp1(k38A)) inhibits mitochondrial fission and Bax accumulation on mitochondria induced by exposure to an NO donor. Although NO is known to cause a bioenergetic crisis, lowering ATP by glycolytic or mitochondrial inhibitors neither induces mitochondrial fission nor Bax foci formation on mitochondria. Taken together, these data indicate that the mitochondrial fission machinery acts upstream of the Bcl-2 family of proteins in neurons challenged with nitrosative stress.
Authors:
H Yuan; A A Gerencser; G Liot; S A Lipton; M Ellisman; G A Perkins; E Bossy-Wetzel
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2006-10-20
Journal Detail:
Title:  Cell death and differentiation     Volume:  14     ISSN:  1350-9047     ISO Abbreviation:  Cell Death Differ.     Publication Date:  2007 Mar 
Date Detail:
Created Date:  2007-02-15     Completed Date:  2007-06-08     Revised Date:  2007-12-03    
Medline Journal Info:
Nlm Unique ID:  9437445     Medline TA:  Cell Death Differ     Country:  England    
Other Details:
Languages:  eng     Pagination:  462-71     Citation Subset:  IM    
Affiliation:
Apoptosis and Cell Death Program, Burnham Institute for Medical Research, La Jolla, CA 92037, USA.
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MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphate / metabolism
Animals
Cell Death
Cells, Cultured
Cerebral Cortex / cytology,  drug effects,  metabolism,  physiology
Glycolysis
Membrane Proteins / metabolism,  physiology
Mitochondria / drug effects,  metabolism*,  physiology,  ultrastructure
Mitochondrial Proteins / metabolism,  physiology
Models, Biological
Neurons / drug effects,  metabolism*,  physiology
Nitric Oxide / pharmacology*
Protein Transport
Rats
Rats, Sprague-Dawley
Transfection
bcl-2-Associated X Protein / metabolism*
bcl-X Protein / metabolism,  physiology
Grant Support
ID/Acronym/Agency:
P01 AI05578/AI/NIAID NIH HHS; P01 AI055789/AI/NIAID NIH HHS; P01 HD29587/HD/NICHD NIH HHS; P41RR04050/RR/NCRR NIH HHS; R01 EY016164/EY/NEI NIH HHS; R01 EY05477/EY/NEI NIH HHS; R01 EY09024/EY/NEI NIH HHS; R01 NS044326/NS/NINDS NIH HHS; R01 NS046994/NS/NINDS NIH HHS; R01 NS047456/NS/NINDS NIH HHS; R01 NS047973/NS/NINDS NIH HHS; R01 NS14718/NS/NINDS NIH HHS; R01 NS44314/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Membrane Proteins; 0/Mitochondrial Proteins; 0/bcl-2-Associated X Protein; 0/bcl-X Protein; 0/mitofusin 1 protein, rat; 10102-43-9/Nitric Oxide; 56-65-5/Adenosine Triphosphate

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