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Mitochondrial cyclic AMP response element-binding protein (CREB) mediates mitochondrial gene expression and neuronal survival.
Lee, Junghee; Kim, Chun-Hyung; Simon, David K; Aminova, Lyaylya R; Andreyev, Alexander Y; Kushnareva, Yulia E; Murphy, Anne N; Lonze, Bonnie E; Kim, Kwang-Soo; Ginty, David D; Ferrante, Robert J; Ryu, Hoon; Ratan, Rajiv R.
Afiliação
  • Lee J; Neurology Department, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
J Biol Chem ; 280(49): 40398-401, 2005 Dec 09.
Article em En | MEDLINE | ID: mdl-16207717
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.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Encéfalo / Regulação da Expressão Gênica / Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico / Mitocôndrias / Neurônios Idioma: En Ano de publicação: 2005 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Encéfalo / Regulação da Expressão Gênica / Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico / Mitocôndrias / Neurônios Idioma: En Ano de publicação: 2005 Tipo de documento: Article