Mitochondrial cyclic AMP response element-binding protein (CREB) mediates mitochondrial gene expression and neuronal survival Academic Article uri icon


MeSH Major

  • Brain
  • Cyclic AMP Response Element-Binding Protein
  • Gene Expression Regulation
  • Mitochondria
  • Neurons


  • 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.

publication date

  • December 9, 2005



  • Academic Article



  • eng

PubMed Central ID

  • PMC2612541

Digital Object Identifier (DOI)

  • 10.1074/jbc.C500140200

PubMed ID

  • 16207717

Additional Document Info

start page

  • 40398

end page

  • 401


  • 280


  • 49