奶油
线粒体
线粒体DNA
生物
DNAJA3公司
环腺苷酸反应元件结合蛋白
细胞生物学
蛋白质亚单位
转录因子
基因表达
线粒体融合
分子生物学
基因
遗传学
作者
Jung-Hee Lee,Chun-Hyung Kim,David K. Simon,Lyaylya R. Aminova,Alexander Y. Andreyev,Yulia E. Kushnareva,Anne N. Murphy,Bonnie E. Lonze,Kwang Soo Kim,David D. Ginty,Robert J. Ferrante,Hoon Ryu,Rajiv R. Ratan
标识
DOI:10.1074/jbc.c500140200
摘要
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.
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