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，也是导致细胞缺陷的主要部位之一 与年龄有关的疾病。尽管其重要性显而易见，但发现的蛋白质中大约有 1/3 没有 知道函数。鲁特实验室的一个主要目标是定义这些蛋白质的一个子集的功能， 特别是那些在真核物种中进化高度保守的物种。我们已经开始了这个 过程并定义了十个线粒体蛋白家族的分子功能。这些已包括 OXPHOS 复合体组装、线粒体质量控制、代谢调节和 其他人。这些发现使我们的实验室和许多其他实验室能够对 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定义以下职能的结合： 以前未研究过的线粒体蛋白，并利用我们以前的发现来更好地研究 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.