Regulation factors in the human energy supplying system.

ATP合成酶（ATP synthase, FoF1）在细胞能量代谢中起核心作用，并通过膜电化学电位和蛋白质合成来调节ATP的维持。为了了解这些，我们研究了FoF1的能量学和合成。由于alpha3beta3gamma复合物是FoF1 F1部分的主要成分，我们对人FoF1 α、β和γ亚基的基因结构进行了测序。这些基因被认为具有没有塔塔盒子的管家基因的共同特征。在人类基因组中，只有一个真正的基因编码α， β和γ亚基。比较这些基因的5'上游区域，可以发现三个共同的序列（CS1、CS2和CS3），表明假定的顺式元件协调了三个亚基基因的表达。多个转录起始位点位于α和β基因起始密码子的上游。α亚基的基因长度为14 kbp，包含12个被11个内含子打断的外显子。在α基因中发现了至少13个Alu重复序列。γ亚基的同工异构体是通过交替剪接产生的，肌肉特异性转录物以盒状方式缺少外显子9 （j . biolchem .）。268: 24950 (1993)；在牛，FEBS快报325:281(1993))。快速的肌肉活动降低了细胞质pH值，这导致了外显子9的排除，这种诱导被环己亚胺和蛋白激酶C抑制剂抑制。相反，高细胞质pH值导致肝型γ的产生（J.Biol.Chem）。269：出版，1994年)。细胞质实验表明，核DNA在线粒体DNA表达中的主导作用（J.Biol.Chem.）。269：出版，1994年)。调节线粒体DNA复制和转录的因子（称为mtTF1）已被证明有两个异构体（生物化学）。Biophys。共同决议，194:544(1993))。

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)).