Horizontal mtDNA Exchange

线粒体DNA水平交换

• 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
• 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

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.

项目总结： 线粒体是细胞质细胞器，由于其在能量中的主要作用，对基本细胞功能至关重要 生产和线粒体功能障碍与许多人类疾病的病因学有关。它们包含 他们自己的基因组(MtDNA)是通过母体传播的。目前的教条认为哺乳动物细胞传递 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， 更出人意料的是，我们的初步研究表明，线粒体和 不是亲子关系的细胞之间的线粒体DNA。这项提议的目的是测试我们的 主要假设水平线粒体DNA转移在正常发育过程中很常见，对维持 或者拯救细胞的新陈代谢潜能。我们的团队试图揭开基因、表观遗传和细胞 管理水平线粒体DNA获取的机制，并找到关于如何、何时以及为什么在 捐献遗体并接受线粒体DNA。最终目标是了解线粒体dna在高能量需求下的稳定性。 器官和组织，尤其是在衰老过程中。我们的研究可能会对我们的 了解线粒体DNA生物学并指导未来治疗方法的发展以维持 通过实验性线粒体转移和替换来保持线粒体基因组的完整性。