Horizontal mtDNA Exchange

线粒体DNA水平交换

基本信息

批准号：
9902293
负责人：
SHOUKHRAT M MITALIPOV
金额：
$ 55.93万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-04-01 至 2024-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9902293
关键词：
Address Adult Age Aging Biology Cell Communication Cell Lineage Cell division Cell physiology Cells Cellular biology Chimera organism Cytoplasmic Organelle DNA Development Diabetes Mellitus Epigenetic Process Etiology Future Genetic Genome Goals Haplotypes Histones Individual Malignant Neoplasms Mammalian Cell Metabolic Mitochondria Mitochondrial DNA Mitotic Mouse Strains Mus Mutation Neurodegenerative Disorders Nuclear Oocytes Organ Parents Pathogenicity Pathologic Patients Physiological Processes Production Reactive Oxygen Species Research Role Source Testing Therapeutic Tissues age related aged base daughter cell embryo cell genome integrity human disease in vivo insight mitochondrial DNA mutation mitochondrial dysfunction mitochondrial genome mutant offspring recombinational repair response single cell analysis stem cells trafficking transgenerational epigenetic inheritance

项目摘要

Project Summary: Mitochondria are cytoplasmic organelles, critical to basic cellular function due to their principal role in energy production and mitochondrial dysfunction is implicated in the etiology of many human diseases. They contain their own genome (mtDNA) that is transmitted maternally. Current dogma holds that mammalian cells transmit their nuclear and mitochondrial genomes exclusively vertically to daughter cells, during cell divisions. However, and rather unexpectedly, our preliminary studies have demonstrated horizontal exchange of mitochondria and mtDNA between cells that are not in a parent-offspring relationship. The objective of this proposal is to test our main hypothesis that horizontal mtDNA transfer is common during normal development and is critical to maintain or rescue the metabolic potential of cells. Our team seeks to uncover genetic, epigenetic and cellular mechanisms governing horizontal mtDNA acquisition and find answers on how, when and why cells within a body donate and accept mtDNA. The ultimate goal is to understand mtDNA stability in high energy-demanding organs and tissues, particularly during aging. Our research will likely have a significant impact on our understanding of mtDNA biology and guide the development of future therapeutic approaches to maintain mitochondrial genome integrity by experimental mitochondrial transfer and replacement.

项目概要：线粒体是细胞质细胞器，由于其在能量方面的主要作用而对基本细胞功能至关重要线粒体的产生和功能障碍与许多人类疾病的病因有关。它们含有他们自己的基因组（mtDNA）是通过母系传播的。目前的教条认为哺乳动物细胞传播在细胞分裂期间，它们的核和线粒体基因组完全垂直于子细胞。然而，出乎意料的是，我们的初步研究表明线粒体和不存在亲子关系的细胞之间的线粒体DNA。该提案的目的是测试我们的主要假设是线粒体DNA水平转移在正常发育过程中很常见，并且对于维持线粒体DNA水平至关重要或拯救细胞的代谢潜力。我们的团队致力于揭示遗传、表观遗传和细胞控制水平 mtDNA 获取的机制，并找到细胞如何、何时以及为什么的答案身体捐赠和接受线粒体DNA。最终目标是了解 mtDNA 在高能量需求下的稳定性器官和组织，特别是在衰老过程中。我们的研究可能会对我们产生重大影响了解 mtDNA 生物学并指导未来治疗方法的开发，以维持通过实验性线粒体转移和替换来保证线粒体基因组的完整性。