GABP transcription factor (nuclear respiratory factor 2) is required for mitochondrial biogenesis.

GABP transcription factor (nuclear respiratory factor 2) is required for mitochondrial biogenesis.
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GABP 转录因子(核呼吸因子 2)是线粒体生物发生所必需的。

DOI:
10.1128/mcb.00492-12
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发表时间:
2014
影响因子:
5.3
通讯作者:
Rosmarin,AlanG
Rosmarin,AlanG
中科院分区:
生物学2区
文献类型:
--
作者:
Yang,Zhong-Fa;Drumea,Karen;Mott,Stephanie;Wang,Junling;Rosmarin,AlanG

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线粒体是膜结合的细胞质细胞器,其作为真核细胞中ATP产生的主要来源。GABP(也称为核呼吸因子2)是一种核E26转化特异性转录因子(ETS),可结合并激活电子传递和氧化磷酸化所需的线粒体基因。我们有条件地删除了Gabpa,这种转录因子复合物的DNA结合成分,从小鼠胚胎成纤维细胞(MEFs)研究Gabp在线粒体生物发生,功能和基因表达中的作用。Gabpα丢失适度降低线粒体质量、ATP产生、氧消耗和线粒体蛋白合成,但不改变线粒体形态、膜电位、细胞凋亡或先前报道为GABP靶点的几个基因的表达。然而,在Gabpα缺失的MEFs中,Tfb1m(一种修饰核糖体rRNA并为线粒体蛋白翻译所需的甲基转移酶)的表达显著降低。我们的结论是,Gabp调节Tfb1m的表达,并发挥了重要的,非冗余的线粒体生物合成的作用。
Mitochondria are membrane-bound cytoplasmic organelles that serve as the major source of ATP production in eukaryotic cells. GABP (also known as nuclear respiratory factor 2) is a nuclear E26 transformation-specific transcription factor (ETS) that binds and activates mitochondrial genes that are required for electron transport and oxidative phosphorylation. We conditionally deleted Gabpa, the DNA-binding component of this transcription factor complex, from mouse embryonic fibroblasts (MEFs) to examine the role of Gabp in mitochondrial biogenesis, function, and gene expression. Gabpα loss modestly reduced mitochondrial mass, ATP production, oxygen consumption, and mitochondrial protein synthesis but did not alter mitochondrial morphology, membrane potential, apoptosis, or the expression of several genes that were previously reported to be GABP targets. However, the expression of Tfb1m, a methyltransferase that modifies ribosomal rRNA and is required for mitochondrial protein translation, was markedly reduced in Gabpα-null MEFs. We conclude that Gabp regulates Tfb1m expression and plays an essential, nonredundant role in mitochondrial biogenesis.