A Comprehensive Proteomic Map of Mammalian Mitochondria

哺乳动物线粒体的综合蛋白质组图谱

基本信息

批准号：
7196012
负责人：
Vamsi Krishna Mootha
金额：
$ 47.09万
依托单位：
MASSACHUSETTS INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-02-01 至 2012-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7196012
关键词：
Affect Aging-Related Process Apoptosis Atlases Candidate Disease Gene Cataloging Catalogs Cell Nucleus Cell physiology Classification Clinical Medicine Complement Complex Computational Biology Cytosol Data Defect Depth Detection Development Disease Equipment and supply inventories Etiology Foundations Functional disorder Genes Genome Genomics Goals Haplotypes Health Heart failure Homeostasis Human Image Inborn Errors of Metabolism Inherited Ions Label Link Maps Measures Metabolic Diseases Methodology Microscopy Mind Mitochondria Mitochondrial Diseases Mitochondrial Proteins Mutation Nerve Degeneration Non-Insulin-Dependent Diabetes Mellitus Nuclear Numbers Organelles Pathogenesis Pathway interactions Pattern Peptides Play Prevention Production Property Protein Biochemistry Proteins Proteomics Research Personnel Resources Role Shapes Source Stable Isotope Labeling Steroids Structure Surveys System Technology Tissues Variant Work base body system cell type gene discovery genome sequencing human disease insight interdisciplinary approach interest lipid metabolism mitochondrial dysfunction neuronal cell body novel programs protein expression tandem mass spectrometry therapeutic target

项目摘要

DESCRIPTION (provided by applicant): Mitochondria are tiny organelles found within virtually all of our body's cells. They control a number of important cellular processes, including energy production, fat metabolism, steroid synthesis, and programmed cell death. Recently, multiple studies have shown that inherited or acquired mitochondrial dysfunction can give rise to a host of rare metabolic disorders, as well as many common diseases, including type 2 diabetes mellitus, heart failure, neurodegeneration, and the aging process itself. Mitochondria are complex structures, consisting of an estimated 1500 proteins. The majority of these proteins are encoded in the cell's nucleus, produced in the cytosol, and then imported into the mitochondrion. At present, we only know about 750 of the estimated 1500 mitochondrial proteins. Because mitochondria contribute to so many rare and common human diseases, it's important that we systematically identify all the proteins that constitute this organelle and begin to understand how they function together in health and in disease. Availability of complete mammalian genome sequences, in combination with new protein detection and microscopy technologies, now provide a special opportunity to systematically and comprehensively identify all the protein components of mammalian mitochondria, as well as how they function together. In the current application, we propose to use a multidisciplinary approach that blends protein biochemistry, computational genomics, and imaging, to construct a protein parts list for mammalian mitochondria. This project will provide an important foundation for systematic approaches to mitochondrial function, which will be extremely important in the coming years as we link its activity to common human diseases, such as type 2 diabetes mellitus. Moreover, the protein catalog that we generate will immediately provide a rich source of candidate disease genes for rare mitochondrial disorders.

描述（由申请人提供）：线粒体是几乎存在于我们身体所有细胞中的微小细胞器。它们控制许多重要的细胞过程，包括能量产生、脂肪代谢、类固醇合成和程序性细胞死亡。最近，多项研究表明，遗传性或获得性线粒体功能障碍可导致一系列罕见的代谢紊乱以及许多常见疾病，包括 2 型糖尿病、心力衰竭、神经退行性变和衰老过程本身。线粒体是复杂的结构，由大约 1500 种蛋白质组成。这些蛋白质大部分在细胞核中编码，在细胞质中产生，然后输入线粒体中。目前，我们只知道大约 1500 种线粒体蛋白中的 750 种。由于线粒体会导致许多罕见和常见的人类疾病，因此系统地识别构成该细胞器的所有蛋白质并开始了解它们如何在健康和疾病中共同发挥作用非常重要。完整的哺乳动物基因组序列的可用性，结合新的蛋白质检测和显微镜技术，现在提供了一个特殊的机会，可以系统地、全面地识别哺乳动物线粒体的所有蛋白质成分，以及它们如何共同发挥作用。在当前的应用中，我们建议使用融合蛋白质生物化学、计算基因组学和成像的多学科方法来构建哺乳动物线粒体的蛋白质部分列表。该项目将为线粒体功能的系统方法提供重要基础，这在未来几年将极其重要，因为我们将其活动与常见的人类疾病（例如 2 型糖尿病）联系起来。此外，我们生成的蛋白质目录将立即提供罕见线粒体疾病候选疾病基因的丰富来源。