De Rasmo Domenico, Signorile Anna, Roca Emilio, Papa Sergio
Department of Medical Biochemistry, Biology and Physics (DIBIFIM), University of Bari, Italy.
FEBS J. 2009 Aug;276(16):4325-33. doi: 10.1111/j.1742-4658.2009.07133.x. Epub 2009 Jul 15.
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.
环磷酸腺苷反应元件结合蛋白（CREB）是高等真核生物中一种普遍存在的转录因子，一旦被磷酸化，就会促进环磷酸腺苷反应元件调控基因的转录。我们研究了CREB的线粒体导入及其对线粒体DNA编码蛋白表达的影响。使用人cDNA构建体在兔网织红细胞裂解物系统中体外合成的[³⁵S]甲硫氨酸标记的CREB，通过膜电位和转位酶外膜复合物（TOM）依赖的过程导入分离的大鼠肝线粒体基质中。导入的CREB导致环磷酸腺苷依赖性促进氧化磷酸化酶复合物线粒体编码亚基的合成。因此，CREB除了进入细胞核外，还从细胞质转移到线粒体，并且当被环磷酸腺苷依赖性蛋白激酶磷酸化时，促进线粒体基因的表达。
