| Bcl-2 family interaction with the mitochondrial morphogenesis machinery. | |
| | |
MedLine Citation:
|
PMID: 20671748 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
The regulation of both mitochondrial dynamics and apoptosis is key for maintaining the health of a cell. Bcl-2 family proteins, central in apoptosis regulation, also have roles in the maintenance of the mitochondrial network. Here we report that Bax and Bak participate in the regulation of mitochondrial fusion in mouse embryonic fibroblasts, primary mouse neurons and human colon carcinoma cells. To assess how Bcl-2 family members may regulate mitochondrial morphogenesis, we determined the binding of a series of chimeras between Bcl-xL and Bax to the mitofusins, mitofusin 1 (Mfn1) and mitofusin 2 (Mfn2). One chimera (containing helix 5 (H5) of Bax replacing H5 of Bcl-xL (Bcl-xL/Bax H5)) co-immunoprecipitated with Mfn1 and Mfn2 significantly better than either wild-type Bax or Bcl-xL. Expression of Bcl-xL/Bax H5 in cells reduced the mobility of Mfn1 and Mfn2 and colocalized with ectopic Mfn1 and Mfn2, as well as endogenous Mfn2 to a greater extent than wild-type Bax. Ultimately, Bcl-xL/Bax H5 induced substantial mitochondrial fragmentation in healthy cells. Therefore, we propose that Bcl-xL/Bax H5 disturbs mitochondrial morphology by binding and inhibiting Mfn1 and Mfn2 activity, supporting the hypothesis that Bcl-2 family members have the capacity to regulate mitochondrial morphology through binding to the mitofusins in healthy cells. |
| | |
Authors:
|
M M Cleland; K L Norris; M Karbowski; C Wang; D-F Suen; S Jiao; N M George; X Luo; Z Li; R J Youle |
Related Documents
:
|
9464838 - Ectopic expression of bcl-2, but not bcl-xl rescues ramos b cells from fas-mediated apo... 19369968 - Vsv virotherapy improves chemotherapy by triggering apoptosis due to proteasomal degrad... 18215418 - The cellular concentration of bcl-2 determines its pro- or anti-apoptotic effect. 16162358 - Nocodazole, a microtubule de-polymerising agent, induces apoptosis of chronic lymphocyt... 18172448 - Primer: making sense of t-cell memory. 17408058 - Effects of astragalus polysaccharides and astragalosides on the phagocytosis of mycobac... |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural Date: 2010-07-30 |
Journal Detail:
|
Title: Cell death and differentiation Volume: 18 ISSN: 1476-5403 ISO Abbreviation: Cell Death Differ. Publication Date: 2011 Feb |
Date Detail:
|
Created Date: 2011-01-10 Completed Date: 2011-04-25 Revised Date: 2011-09-26 |
Medline Journal Info:
|
Nlm Unique ID: 9437445 Medline TA: Cell Death Differ Country: England |
Other Details:
|
Languages: eng Pagination: 235-47 Citation Subset: IM |
Affiliation:
|
Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Apoptosis Cell Line Fibroblasts / metabolism GTP Phosphohydrolases / genetics, metabolism Humans Immunoprecipitation Mice Mitochondria / metabolism*, ultrastructure Neurons / metabolism Protein Structure, Tertiary Proto-Oncogene Proteins c-bcl-2 / metabolism* bcl-2 Homologous Antagonist-Killer Protein / genetics, metabolism bcl-2-Associated X Protein / genetics, metabolism bcl-X Protein / genetics, metabolism |
| Grant Support | |
ID/Acronym/Agency:
|
R01 GM076237-05/GM/NIGMS NIH HHS; R01 GM083131-01A1/GM/NIGMS NIH HHS; R01-GM083131/GM/NIGMS NIH HHS; R01-GM76237/GM/NIGMS NIH HHS; Z01 MH002881-01/MH/NIMH NIH HHS; Z01 NS002859-17/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Proto-Oncogene Proteins c-bcl-2; 0/bcl-2 Homologous Antagonist-Killer Protein; 0/bcl-2-Associated X Protein; 0/bcl-X Protein; EC 3.6.1.-/GTP Phosphohydrolases; EC 3.6.1.-/Mfn1 protein, mouse; EC 3.6.1.-/Mfn2 protein, mouse |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Maximal adamantyl-substituted retinoid-related molecule-induced apoptosis requires NF-?B noncanonica...
Next Document: Serine 312 phosphorylation is dispensable for wild-type p53 functions in vivo.