EXPRESSION OF MITOCHONDRIAL RIBOSOMAL PROTEINS IN YEAST

这项建议的长期目标是理解 线粒体的过程及其调控方式 通过发育和生理刺激。作为必要的一步 为了实现这些目标，这些研究将审查 双重遗传来源的线粒体复合体的生物合成 确定这样一个复合体的组成部分是否协调一致 表达。酿酒酵母的线粒体核糖体就是这样一种 很复杂。核编码线粒体的表达 将对核糖体蛋白进行检查，以确定它们最终的 稳态水平与这些核糖体成分是平衡的 它们被编码在线粒体中。一项关于 核编码生物合成的调控问题 线粒体核糖体蛋白要求探针可用 检测大鼠肺组织中mRNA和蛋白质的表达。 干扰核糖体成分合成的条件。 为此，线粒体核糖体蛋白将被提纯并 两者都用来分离它们相应的基因并提高 抗体。将尝试在体内过度表达这些基因 酵母细胞相对于其他核糖体成分。如果稳定的- 线粒体核糖体的任一编码基因的状态水平 蛋白质或核糖体蛋白质本身不能 大大高于其他组件， 调节其表达以实现平衡的机制 表达方式将会确定。 线粒体在细胞新陈代谢中起着核心作用 线粒体异常，并与许多 病理情况包括某些甲状腺肿瘤， 甲状旁腺和脑下垂体。最近的研究结果表明 线粒体发育调节中的损伤 生物发生可导致严重的临床疾病和死亡。AS 这样，线粒体的生物发生及其调节可以是直接的或 导致许多疾病状态的因素。这两种技术的结合 基础研究，如本提案中描述的研究和 在过去，临床研究已经成功地用于 疾病的治疗管理。预计这将是 组合将继续，并可能在未来用于 探索治疗管理的方法 线粒体肌病。

The long range goals of this proposal are to understand the process of mitochondrial and how this process may be regulated by developmental and physiological stimuli. As a necessary step in achieving these goals these studies will examine the biosynthesis of a mitochondrial complex of duel genetic origin to determine if the components of such a complex are coordinately expressed. The mitochondrial ribosome of S. cerevisiae is such a complex. The expression of nuclear-encoded mitochondrial ribosomal proteins will be examined to determine how their final steady-state levels are balanced with those ribosomal components that are coded in the mitochondria. An examination of the regulatory aspects of the biosynthesis of nuclear-encoded mitochondrial ribosomal proteins requires that probes be available to measure the expressioin of both mRNA and protein under conditions that perturb the synthesis of ribosomal components. To this end, mitochondrial ribosomal proteins will be purified and used both to isolate their corresponding genes and raise antibodies. Attempts will be made to overexpress these genes in yeast cells relative to other ribosomal components. If the steady- state levels of either mRNA coding for mitochondrial ribosomal proteins or the ribosomal proteins themselves cannot be substantially increased above that of other components, the mechanisms that regulate their expression to achieve balanced expression will be determined. Mitochondria play a central role in cellular metabolism and mitochondrial abnormalities and have been associated with many pathological conditions including certain neoplasms of the thyroid, parathyroid, and pituitary. More recent findings have suggested that lesions in the developmental regulation of mitochondrial biogenesis can lead to severe clinical disorders and death. As such, mitochondrial biogenesis and its regulation may be direct or contributing factors to many disease states. The combination of basic research such as that described within this proposal and clinical studies have been successfully used in the past for the therapeutic managements of diseases. It is anticipated that this combination will continue and may be used in the future to explore approaches to the therapeutic management of mitochondrial myopathies.