Document Detail


Translational control of mitochondrial energy production mediates neuron morphogenesis.
MedLine Citation:
PMID:  23217258     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Mitochondrial energy production is a tightly regulated process involving the coordinated transcription of several genes, catalysis of a plethora of posttranslational modifications, and the formation of very large molecular supercomplexes. The regulation of mitochondrial activity is particularly important for the brain, which is a high-energy-consuming organ that depends on oxidative phosphorylation to generate ATP. Here we show that brain mitochondrial ATP production is controlled by the cytoplasmic polyadenylation-induced translation of an mRNA encoding NDUFV2, a key mitochondrial protein. Knockout mice lacking the Cytoplasmic Polyadenylation Element Binding protein 1 (CPEB1) have brain-specific dysfunctional mitochondria and reduced ATP levels, which is due to defective polyadenylation-induced translation of electron transport chain complex I protein NDUFV2 mRNA. This reduced ATP results in defective dendrite morphogenesis of hippocampal neurons both in vitro and in vivo. These and other results demonstrate that CPEB1 control of mitochondrial activity is essential for normal brain development.
Authors:
Aparna Oruganty-Das; Teclise Ng; Tsuyoshi Udagawa; Eyleen L K Goh; Joel D Richter
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cell metabolism     Volume:  16     ISSN:  1932-7420     ISO Abbreviation:  Cell Metab.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-10     Completed Date:  2013-05-22     Revised Date:  2013-12-11    
Medline Journal Info:
Nlm Unique ID:  101233170     Medline TA:  Cell Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  789-800     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphate / metabolism*
Animals
Cells, Cultured
Electron Transport Complex I / metabolism
Female
Gene Expression
Mice
Mice, Inbred C57BL
Mice, Knockout
Mitochondria / metabolism*
Morphogenesis
NADH Dehydrogenase / genetics,  metabolism
Neurons / cytology,  metabolism*
Polyadenylation
Protein Biosynthesis / genetics*
RNA Interference
RNA, Messenger / metabolism
RNA, Small Interfering / metabolism
Transcription Factors / antagonists & inhibitors,  genetics,  metabolism
mRNA Cleavage and Polyadenylation Factors / antagonists & inhibitors,  genetics,  metabolism
Grant Support
ID/Acronym/Agency:
AG30323/AG/NIA NIH HHS; DK32520/DK/NIDDK NIH HHS; GM46779/GM/NIGMS NIH HHS; HD37267/HD/NICHD NIH HHS; R01 AG030323/AG/NIA NIH HHS; R01 GM046779/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Cpeb1 protein, mouse; 0/RNA, Messenger; 0/RNA, Small Interfering; 0/Transcription Factors; 0/mRNA Cleavage and Polyadenylation Factors; 8L70Q75FXE/Adenosine Triphosphate; EC 1.6.5.3/Electron Transport Complex I; EC 1.6.99.3/NADH Dehydrogenase
Comments/Corrections
Comment In:
Nat Rev Neurosci. 2013 Feb;14(2):80-1   [PMID:  23271113 ]

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


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