Document Detail


The dynamin-related GTPase Opa1 is required for glucose-stimulated ATP production in pancreatic beta cells.
MedLine Citation:
PMID:  21551073     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Previous studies using in vitro cell culture systems have shown the role of the dynamin-related GTPase Opa1 in apoptosis prevention and mitochondrial DNA (mtDNA) maintenance. However, it remains to be tested whether these functions of Opa1 are physiologically important in vivo in mammals. Here, using the Cre-loxP system, we deleted mouse Opa1 in pancreatic beta cells, in which glucose-stimulated ATP production in mitochondria plays a key role in insulin secretion. Beta cells lacking Opa1 maintained normal copy numbers of mtDNA; however, the amount and activity of electron transport chain complex IV were significantly decreased, leading to impaired glucose-stimulated ATP production and insulin secretion. In addition, in Opa1-null beta cells, cell proliferation was impaired, whereas apoptosis was not promoted. Consequently, mice lacking Opa1 in beta cells develop hyperglycemia. The data suggest that the function of Opa1 in the maintenance of the electron transport chain is physiologically relevant in beta cells.
Authors:
Zhongyan Zhang; Nobunao Wakabayashi; Junko Wakabayashi; Yasushi Tamura; Woo-Jin Song; Sam Sereda; Pascaline Clerc; Brian M Polster; Susan M Aja; Mikhail V Pletnikov; Thomas W Kensler; Orian S Shirihai; Miho Iijima; Mehboob A Hussain; Hiromi Sesaki
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-05-05
Journal Detail:
Title:  Molecular biology of the cell     Volume:  22     ISSN:  1939-4586     ISO Abbreviation:  Mol. Biol. Cell     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-07-04     Completed Date:  2011-12-12     Revised Date:  2013-07-16    
Medline Journal Info:
Nlm Unique ID:  9201390     Medline TA:  Mol Biol Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2235-45     Citation Subset:  IM    
Affiliation:
Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
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MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphate / biosynthesis*,  metabolism
Animals
Apoptosis / physiology
Cell Proliferation
DNA, Mitochondrial / metabolism
Dynamins / metabolism*
Electron Transport Complex IV / metabolism
GTP Phosphohydrolases / deficiency,  genetics,  metabolism*
Glucose / metabolism*
Glucose Intolerance / metabolism
Hyperglycemia / metabolism,  pathology
Insulin / metabolism
Insulin-Secreting Cells / cytology,  enzymology,  metabolism*
Mice
Mice, Inbred C57BL
Mice, Transgenic
Mitochondria / metabolism
Receptor-Interacting Protein Serine-Threonine Kinases / metabolism
Grant Support
ID/Acronym/Agency:
DK079639/DK/NIDDK NIH HHS; DK081472/DK/NIDDK NIH HHS; GM084015/GM/NIGMS NIH HHS; GM089853/GM/NIGMS NIH HHS; R01 DK035914/DK/NIDDK NIH HHS; R01 GM084015/GM/NIGMS NIH HHS; R01 GM089853/GM/NIGMS NIH HHS; R01 GM089853-01A1/GM/NIGMS NIH HHS; R01 GM089853-02/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/DNA, Mitochondrial; 0/Insulin; 50-99-7/Glucose; 56-65-5/Adenosine Triphosphate; EC 1.9.3.1/Electron Transport Complex IV; EC 2.7.1.-/Ripk2 protein, mouse; EC 2.7.11.1/Receptor-Interacting Protein Serine-Threonine Kinases; EC 3.6.1.-/GTP Phosphohydrolases; EC 3.6.1.-/Opa1 protein (GTPase), mouse; EC 3.6.5.5/Dynamins
Comments/Corrections

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