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.

项目摘要： 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 生产和线粒体功能障碍与许多人类疾病的病因有关。它们包含 他们自己的基因组（mtDNA）是在母亲传播的。当前的教条认为哺乳动物细胞会传播 在细胞分裂期间，它们的核和线粒体基因组仅垂直垂直于子细胞。然而， 相当出乎意料的是，我们的初步研究表明了线粒体和 不在父源性关系中的细胞之间的mtDNA。该提议的目的是测试我们 水平mtDNA转移在正常发育过程中很常见，对维持至关重要的主要假设是 或挽救细胞的代谢潜力。我们的团队试图发现遗传，表观遗传和细胞 管理水平mtDNA获取的机制，并找到有关如何，何时以及为什么在一个内部的细胞 身体捐赠并接受mtDNA。最终目标是了解高能需求中的mtDNA稳定性 器官和组织，特别是在衰老期间。我们的研究可能会对我们的 了解mtDNA生物学并指导未来治疗方法的发展 线粒体基因组完整性通过实验性线粒体转移和替换。

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