cAMP response element-binding protein (CREB) is imported into mitochondria and promotes protein synthesis.
The cAMP response element-binding protein (CREB) is a ubiquitous transcription factor in the higher eukaryotes that, once phosphorylated, promotes transcription of cAMP response element-regulated genes. We have studied the mitochondrial import of CREB and its effect on the expression of mtDNA-encoded proteins. [(35)S]Methionine-labelled CREB, synthesized in vitro in the Rabbit Reticulocyte Lysate system using a construct of the human cDNA, was imported into the matrix of isolated rat liver mitochondria by a membrane potential and TOM complex-dependent process. The imported CREB caused cAMP-dependent promotion of the synthesis of mitochondrially encoded subunits of oxidative phosphorylation enzyme complexes. Thus, CREB moves from the cytosol to mitochondria, in addition to the nucleus, and, when phosphorylated by cAMP-dependent protein kinase, promotes the expression of mitochondrial genes.
De Rasmo
Domenico
D
Department of Medical Biochemistry, Biology and Physics (DIBIFIM), University of Bari, Italy.
Signorile
Anna
A
Roca
Emilio
E
Papa
Sergio
S
D000818:Animals; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism* / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000096:biosynthesis*; D010085:Oxidative Phosphorylation; D010766:Phosphorylation; D014176:Protein Biosynthesis; D021381:Protein Transport; D051381:Rats
D017362:Cyclic AMP Response Element-Binding Protein; D024101:Mitochondrial Proteins