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Regulation factors in the human energy supplying system.

人体能量供应系统的调节因素。

基本信息

批准号：
02404027
负责人：
KAGAWA Yasuo
金额：
$ 15.62万
依托单位：
JICHI MEDICAL SCHOOL
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (A)
财政年份：
1990
资助国家：
日本
起止时间：
1990 至 1993
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-02404027/
关键词：
ATP synthase transcription factor alternate splicing subunit composition transcription control mitochondria F1-ATPase control by pH 協調発現 F_1・ATDアーゼ高次構造ミトコンドリア脳筋症 ATP synthase Bioenergetics mitochondria transcriptional contr

项目摘要

ATP synthase (FoF1) plays a central role in cellular energy metabolism, and is regulated to maintain ATP via membrane electrochemical potential and protein synthesis. To understand these, both the energetics and synthesis of FoF1 were studied. The gene structures of the alpha, beta and gamma subunits of human FoF1 were sequenced, because alpha3beta3gamma complex is the major component of F1 portion of FoF1. These genes were whown to have common features of house keeping genes which have no TATA box. There are only one each bona fide gene encoding for the alpha, beta and gamma subunits in a human genome. Comparison of the 5'-upstream regions of these genes indicated three common sequences (CS1, CS2 and CS3), suggesting that putative cis-elements coordinate the expressions of the three subunits genes. The multiple transcription initiation sites were found upstream of the initiation codon of the alpha and beta genes. The gene for the alpha subunit was 14 kbp in length and contained 12 exons interrupted by 11 introns. At least 13 Alu repeating sequences were found in the alpha gene. The isoforms of the gamma subunit were generated by alternate splicing, and the muscle specific transcript lacks exon 9 in a casette fashion (J.Biol.Chem. 268 : 24950 (1993) ; in bovine, FEBS Lett. 325 : 281 (1993)). A rapid muscle activity lowers cytoplasmic pH, which induced exclusion of exon 9, and this induction was inhibited by cycloheximide and protein kinase C inhibitors. In contrast, a high cytoplasmic pH resulte in the production of liver type gamma (J.Biol.Chem. 269 : in press, 1994). The dominating function of nuclear DNA over the mitochondrial DNA expression has been shown by the cytoplast experiments (J.Biol.Chem. 269 : in press, 1994). The factor regulating both replication and transcription of the mitochondrial DNA (called mtTF1) has been shown to have two isofoms (Biochem. Biophys. Res. Commun. 194 : 544 (1993)).

三磷酸腺苷合成酶(FoF1)在细胞能量代谢中起核心作用，通过膜电化学势和蛋白质合成调节维持三磷酸腺苷。为了理解这一点，我们对FoF1的热力学和合成进行了研究。由于α3β3伽马复合体是FoF1基因F1部分的主要成分，因此对人FoF1的α、β和伽马亚基的基因结构进行了测序。这些基因具有看家基因的共同特征，这些基因没有TATA盒。在人类基因组中，每个真正的基因只有一个编码阿尔法、贝塔和伽马亚基。比较这些基因的5‘-上游区域，发现了三个共同的序列(CS1、CS2和CS3)，这表明可能的顺式元件协调了这三个亚基基因的表达。在α基因和β基因起始密码子的上游发现了多个转录起始点。α亚基基因全长14kbp，包含12个外显子和11个内含子。在α基因中至少发现了13个Alu重复序列。伽马亚基的异构体是通过交替剪接产生的，而肌肉特异性转录物以干酪方式缺乏外显子9(J.Biol.Chem。268：24950(1993年)；在牛，FEBS Lett。325：281(1993))。快速的肌肉活动降低了细胞质的pH，从而导致外显子9的排除，这种诱导可以被放线菌亚胺和蛋白激酶C抑制剂抑制。相反，较高的细胞质pH导致肝型伽马的产生(J.Biol.Chem.269：新闻出版，1994年)。核DNA在线粒体DNA表达中的主导作用已被细胞质实验(J.Biol.Chem.269：新闻出版，1994年)。调控线粒体DNA复制和转录的因子(称为mtTF1)已被证明有两个异构体(Biochem)。生物群落。[中英文摘要]Re.Commun.194：544(1993))。