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Mitochondrial Cyclic AMP Response Element-binding Protein (CREB) Mediates Mitochondrial Gene Expression and Neuronal Survival.

Authors :
Junghee Lee
Chun-Hyung Kim
Simon, David K.
Aminova, Lyaylya R.
Andreyev, Alexander V.
Kushnareva, Yulia E.
Murphy, Anne N.
Lonze, Bonnie E.
Kwang-Soo Kim
Ginty, David D.
Ferrante, Robert J.
Hoon Ryu
Ratan, Rajiv R.
Source :
Journal of Biological Chemistry. 12/9/2005, Vol. 280 Issue 49, p40398-40401. 4p. 4 Graphs.
Publication Year :
2005

Abstract

Cyclic AMP response element-binding protein (CREB) is a widely expressed transcription factor whose role in neuronal protection is now well established. Here we report that CREB is present in the mitochondrial matrix of neurons and that it binds directly to cyclic AMP response elements (CREs) found within the mitochondrial genome. Disruption of CREB activity in the mitochondria decreases the expression of a subset of mitochondrial genes, including the ND5 subunit of complex I, down-regulates complex I-dependent mitochondrial respiration, and increases susceptibility to 3-nitropropionic acid, a mitochondrial toxin that induces a clinical and pathological phenotype similar to Huntington disease. These results demonstrate that regulation of mitochondrial gene expression by mitochondrial CREB, in part, underlies the protective effects of CREB and raise the possibility that decreased mitochondrial CREB activity contributes to the mitochondrial dysfunction and neuronal loss associated with neurodegenerative disorders. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00219258
Volume :
280
Issue :
49
Database :
Academic Search Index
Journal :
Journal of Biological Chemistry
Publication Type :
Academic Journal
Accession number :
19523881
Full Text :
https://doi.org/10.1074/jbc.C500140200