Mitochondrial Biochemistry: From Mechanisms to Disease

项目摘要/摘要 线粒体是细胞能量的主要来源，也是导致 与年龄相关的疾病。尽管有明显的重要性，但发现的蛋白质中约有三分之一没有 了解功能。罗特实验室的一个主要目标是确定这些蛋白质的子集的功能， 尤其是那些在真核物种中进化高度保守的基因。我们已经开始这样做了 并确定了10个线粒体蛋白家族的分子功能。这些措施包括 OXPHOS复合体组装、线粒体质量控制、代谢调节和调控的重要因素 其他。这些发现使我们的实验室和其他许多人对 人类正常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。拟议的未来活动是我们继续努力界定以下各项职能的综合结果 以前没有研究过的线粒体蛋白质，并利用我们之前的发现 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.