Horizontal mtDNA Exchange

线粒体DNA水平交换

• 批准号: 10584513
• 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/10584513
• 关键词: 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; Genetic Recombination; Genome; Goals; Haplotypes; Histones; Individual; Malignant Neoplasms; Mammalian Cell; Metabolic; Mitochondria; Mitochondrial DNA; 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; blastomere structure; daughter cell; embryo cell; genome integrity; heteroplasmy; human disease; in vivo; insight; mitochondrial DNA mutation; mitochondrial dysfunction; mitochondrial genome; mutant; offspring; postmitotic; repaired; response; single cell analysis; stem cells; trafficking; transgenerational epigenetic inheritance; transmission process

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，由于其在能量中的主要作用，对基本细胞功能至关重要 产生和线粒体功能障碍与许多人类疾病的病因学有关。它们含有 他们自己的基因组（mtDNA）是由母体传递的。目前的理论认为哺乳动物细胞 在细胞分裂期间，它们的核和线粒体基因组专门垂直于子细胞。然而，在这方面， 出乎意料的是，我们的初步研究已经证明了线粒体的水平交换， 线粒体DNA在没有亲子关系的细胞之间。这项建议的目的是测试我们的 一个主要的假设，水平mtDNA转移在正常发育过程中是常见的，并且对维持 或拯救细胞的代谢潜能。我们的团队致力于揭示遗传学、表观遗传学和细胞学 控制水平mtDNA获取的机制，并找到答案，如何，何时以及为什么细胞在一个 身体捐赠和接受mtDNA。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的研究产生重大影响。 理解线粒体DNA生物学，并指导未来治疗方法的发展，以维持 线粒体基因组完整性的实验线粒体转移和替换。

项目成果

Haploidy in somatic cells is induced by mature oocytes in mice.

• DOI: 10.1038/s42003-022-03040-5
• 发表时间: 2022-01-25
• 期刊: Communications biology
• 影响因子: 5.9
• 作者: Lee Y;Trout A;Marti-Gutierrez N;Kang S;Xie P;Mikhalchenko A;Kim B;Choi J;So S;Han J;Xu J;Koski A;Ma H;Yoon JD;Van Dyken C;Darby H;Liang D;Li Y;Tippner-Hedges R;Xu F;Amato P;Palermo GD;Mitalipov S;Kang E
• 通讯作者: Kang E

Horizontal mtDNA transfer between cells is common during mouse development.

• DOI: 10.1016/j.isci.2022.103901
• 发表时间: 2022-03-18
• 期刊: iScience
• 影响因子: 5.8
• 作者: Marti Gutierrez N;Mikhalchenko A;Ma H;Koski A;Li Y;Van Dyken C;Tippner-Hedges R;Yoon D;Liang D;Hayama T;Battaglia D;Kang E;Lee Y;Barnes AP;Amato P;Mitalipov S
• 通讯作者: Mitalipov S