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：
7570629
负责人：
Vamsi Krishna Mootha
金额：
$ 12.19万
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 2009-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7570629
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 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 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 mammalian genome 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）：线粒体几乎在我们体内的所有细胞中都发现了细小的细胞器。他们控制了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，遗传或获得的线粒体功能障碍会导致许多罕见的代谢疾病以及许多常见疾病，包括2型糖尿病，心力衰竭，神经变性和衰老过程本身。线粒体是复杂的结构，由估计的1500种蛋白质组成。这些蛋白的大多数是在细胞核中编码的，在细胞质中产生，然后进口到线粒体中。目前，我们只知道估计的1500个线粒体蛋白中约有750个。由于线粒体有助于许多罕见和常见的人类疾病，因此我们必须系统地识别所有构成该细胞器的蛋白质并开始了解它们在健康和疾病中的作用，这一点很重要。现在，完整的哺乳动物基因组序列与新的蛋白质检测和显微镜技术相结合，现在为系统和全面地识别哺乳动物线粒体的所有蛋白质成分提供了特殊的机会，以及它们如何共同发挥作用。在当前的应用中，我们建议使用将蛋白质生物化学，计算基因组学和成像融合的多学科方法来构建哺乳动物线粒体的蛋白质零件清单。该项目将为线粒体功能的系统方法提供一个重要的基础，这在未来几年将其活动与常见的人类疾病（例如2型糖尿病）联系起来非常重要。此外，我们生成的蛋白质目录将立即为罕见的线粒体疾病提供丰富的候选疾病基因。