Mitochondrial Biochemistry: From Mechanisms to Disease

项目概要/摘要 线粒体是细胞能量的主要来源，也是导致细胞损伤的主要缺陷部位之一。 与年龄有关的疾病尽管有明显的重要性，但在那里发现的大约1/3的蛋白质没有 知道功能。Rutter实验室的一个主要目标是确定这些蛋白质的一个子集的功能， 特别是那些在真核生物中高度进化保守的基因。我们已经开始了 研究并定义了10个线粒体蛋白家族的分子功能。其中包括 OXPHOS复合物组装、线粒体质量控制、代谢调节和 他人这些发现使我们的实验室和其他许多实验室对 正常人类生理学和疾病病理生理学，包括发现两种新的人类疾病 基因.拟议的未来活动包括继续努力确定 以前未研究的线粒体蛋白质，并利用我们以前的发现， 了解线粒体生物学及其生理表现。

Project Summary/Abstract Mitochondria are the major source of cellular energy and are also one of the major sites of defects leading to age-related disorders. In spite of the obvious importance, roughly 1/3 of the proteins found there have no know function. One major goal of the Rutter laboratory is to define the functions of a subset of these proteins, particularly those that are highly evolutionarily conserved across eukaryotic species. We have begun this process and have defined the molecular functions of ten mitochondrial protein families. These have included important factors for OXPHOS complex assembly, mitochondrial quality control, metabolic regulation and others. These discoveries have enabled our laboratory and many others to develop new understanding of normal human physiology and disease pathophysiology, including the discovery of two new human disease genes. The proposed future activities are a combination of continuing our efforts to define the functions of previously unstudied mitochondrial proteins and leveraging our previous discoveries toward a better understanding of mitochondrial biology and its physiological manifestations.