Characterization of transcriptionally regulated genes

转录调控基因的表征

• 批准号: 6325079
• 负责人: ELIZABETH A CRAIG
• 金额: $ 29.54万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 1980
• 资助国家: 美国
• 起止时间: 1980-04-01 至 2005-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6325079
• 关键词: Saccharomyces cerevisiae; fungal genetics; fungal proteins; heat shock proteins; intracellular transport; iron metabolism; mitochondria; mitochondrial DNA; mitochondrial membrane; molecular chaperones; protein biosynthesis; protein folding; protein structure function; protein transport

Mitochondria are essential, complex organelles of eucaryotic organisms required for a variety of metabolic processes including the generation of energy by oxidative phosphorylation. Biogenesis and maintenance of mitochondria requires the function of molecular chaperones such as Hsp7O. Our long term goal is to understand the mechanism of action of molecular chaperones within mitochondria using S. cerevisiae as a model system. Using genetic and biochemical approaches the analysis of the roles of mitochondrial chaperones of the Hsp7O and Hsp4O classes in the processes of protein translocation, folding and assembly of mitochondrial proteins will be continued. These studies are relevant to issues of human health, as certain human tissues, such as brain, heart, muscle and kidney, are particularly dependent on efficient mitochondrial function. Pathological effects caused by reduced bioenergetic capacity have been found to be caused by mutations in both mitochondrial and human DNA in human populations. In addition, one of the mitochondrial Hsp7Os has been implicated in the maturation of the homologue of human frataxin, which is associated with the neurodegenerative disease Freidrich's ataxia. Ssc1, an Hsp7O of the mitochondrial matrix, is an essential component of the apparatus required for translocation of proteins from the cytosol. Ssc 1 is tethered to the import channel via its interaction with an essential peripheral component of the channel, Tim44. Mge 1, an essential nucleotide release factor for Ssc 1, is also associated with Ssc1 at the import channel. Ssc1, an Hsp4O Mdjl, and the nucleotide exchange factor Mgel are thought to facilitate folding of imported proteins. This proposal is designed to understand the pathway of Ssc1 function in translocation of proteins across the mitochondnal proteins and their subsequent folding in the matrix. Ssq1 and Jaci are additional Hsp7Os and Hsp4Os, respectively, of the mitochondrial matrix. A role for Ssq1 in the regulation of iron metabolism and/or the assembly of Fe-S centers is indicated. Our goal is to understand the function(s) of Ssq1 in mitochondria and to provide insight into the cellular process(es) in which Ssql acts. The primary and secondary effects of the lack of Ssql function, focusing on iron metabolism, including its role in the maturation of Yfh 1, the yeast homologue of frataxin, and assembly of Fe-S clusters will be determined using a combination of genetic and biochemical techniques.

线粒体是真核生物的重要的复杂细胞器， 生物体所需的各种代谢过程，包括 通过氧化磷酸化产生能量。生物发生和维持 线粒体的功能需要分子伴侣如Hsp 7 O的作用。 我们的长期目标是了解分子的作用机制， 线粒体内的伴侣蛋白，使用S.酿酒酵母作为模型系统。 利用遗传学和生物化学的方法， Hsp 7 O和Hsp 4 O类的线粒体伴侣蛋白在 线粒体蛋白质的移位、折叠和组装将是 持续期间内的这些研究与人类健康问题有关， 人体组织，例如脑、心脏、肌肉和肾，特别 依赖于有效的线粒体功能。引起的病理效应 已经发现生物能量能力的降低是由两种基因的突变引起的， 线粒体和人类DNA的基因组。此外， 线粒体Hsp 70参与了Hsp 70同源物的成熟， 人共济失调蛋白，与神经退行性疾病相关 Freidrich共济失调。 Ssc 1是线粒体基质的Hsp 7 O，是线粒体的重要组成部分。 蛋白质从胞质中转移所需的装置。Ssc 1是 通过与重要外围设备的相互作用， 频道的组成部分，Tim 44。必需的核苷酸释放因子Mge 1 对于Ssc 1，也与导入通道处的Ssc 1相关联。Ssc1，Hsp4O Mdjl和核苷酸交换因子Mgel被认为促进折叠 进口蛋白质。本提案旨在了解 Ssc 1在蛋白质跨线粒体蛋白质的移位中起作用， 它们在基质中的后续折叠。 Ssq 1和Jac 1分别是Hsp 70和Hsp 40的另外的Hsp 70和Hsp 40， 线粒体基质Ssq 1在铁代谢调节中的作用 和/或指示Fe-S中心的组装。我们的目标是了解 Ssq 1在线粒体中的功能，并提供对细胞 Ssql在其中起作用的进程。缺乏的主要和次要影响 的Ssql功能，侧重于铁代谢，包括其在 Yfh 1的成熟，Frataxin的酵母同系物，和Fe-S的组装 聚类将使用遗传和生物化学的组合来确定， 技术.