• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Nature >Mitochondrial and nuclear DNA matching shapes metabolism and healthy ageing
【24h】

Mitochondrial and nuclear DNA matching shapes metabolism and healthy ageing

机译：线粒体和核DNA匹配塑造新陈代谢和健康衰老

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Human mitochondrial DNA (mtDNA) shows extensive within-population sequence variability(1). Many studies suggest that mtDNA variants may be associated with ageing or diseases(2-4), although mechanistic evidence at the molecular level is lacking(5,6). Mitochondrial replacement has the potential to prevent transmission of disease-causing oocyte mtDNA. However, extension of this technology requires a comprehensive understanding of the physiological relevance of mtDNA sequence variability and its match with the nuclear-encoded mitochondrial genes. Studies in conplastic animals(7-9) allow comparison of individuals with the same nuclear genome but different mtDNA variants, and have provided both supporting and refuting evidence that mtDNA variation influences organismal physiology. However, most of these studies did not confirm the conplastic status, focused on younger animals, and did not investigate the full range of physiological and phenotypic variability likely to be influenced by mitochondria. Here we systematically characterized conplastic mice throughout their lifespan using transcriptomic, proteomic, metabolomic, biochemical, physiological and phenotyping studies. We show that mtDNA haplotype profoundly influences mitochondrial proteostasis and reactive oxygen species generation, insulin signalling, obesity, and ageing parameters including telomere shortening and mitochondrial dysfunction, resulting in profound differences in health longevity between conplastic strains.
机译：人类线粒体DNA（mtDNA）在人群中具有广泛的序列变异性（1）。许多研究表明，尽管缺乏分子水平的机械证据（5,6），但mtDNA变异可能与衰老或疾病有关（2-4）。线粒体替代具有预防致病卵母细胞mtDNA传播的潜力。但是，这项技术的扩展要求全面了解mtDNA序列变异性的生理相关性及其与核编码线粒体基因的匹配性。对合成动物的研究（7-9）允许比较具有相同核基因组但具有不同mtDNA变异体的个体，并提供了支持和反驳的证据，证明mtDNA变异会影响机体生理。但是，这些研究大多数都没有确认可塑性状态，而是针对年轻的动物，也没有研究可能受线粒体影响的全部生理和表型变异性。在这里，我们使用转录组学，蛋白质组学，代谢组学，生化，生理学和表型研究系统地对整形小鼠的整个生命进行了表征。我们表明，mtDNA单倍型深刻影响线粒体蛋白稳态和活性氧的产生，胰岛素信号传导，肥胖和衰老参数，包括端粒缩短和线粒体功能障碍，导致合并菌株之间健康寿命的深刻差异。

著录项

  • 来源
    《Nature》 |2016年第7613期|561-565|共5页
  • 作者

    Latorre-Pellicer Ana; Moreno-Loshuertos Raquel; Victoria Lechuga-Vieco Ana; Sanchez-Cabo Fatima; Torroja Carlos; Acin-Perez Rebeca; Calvo Enrique; Aix Esther; Gonzalez-Guerra Andres; Logan Angela; Luisa Bernad-Miana Maria; Romanos Eduardo; Cruz Raquel; Cogliati Sara; Sobrino Beatriz; Carracedo Angel; Perez-Martos Acisclo; Fernandez-Silva Patricio; Ruiz-Cabello Jesus; Murphy Michael P.; Flores Ignacio; Vazquez Jesus; Antonio Enriquez Jose;

  • 作者单位

    Ctr Nacl Invest Cardiovasc Carlos III, Madrid 28029, Spain|Univ Santiago de Compostela, CIBERER, Grp Med Xenom, Santiago De Compostela 15782, Spain;

    Univ Zaragoza, Dept Bioquim & Biol Mol & Celular, E-50009 Zaragoza, Spain;

    Ctr Nacl Invest Cardiovasc Carlos III, Madrid 28029, Spain|CIBERES, C Melchor Fernandez Almagro 3, Madrid 28029, Spain;

    Ctr Nacl Invest Cardiovasc Carlos III, Madrid 28029, Spain;

    Ctr Nacl Invest Cardiovasc Carlos III, Madrid 28029, Spain;

    Ctr Nacl Invest Cardiovasc Carlos III, Madrid 28029, Spain;

    Ctr Nacl Invest Cardiovasc Carlos III, Madrid 28029, Spain;

    Ctr Nacl Invest Cardiovasc Carlos III, Madrid 28029, Spain;

    Ctr Nacl Invest Cardiovasc Carlos III, Madrid 28029, Spain;

    MRC, Mitochondrial Biol Unit, Hills Rd, Cambridge CB2 0XY, England;

    Inst Aragones Ciencias Salud, SAI Biomed & Biomat & Phenotyp Unit, Zaragoza 50009, Spain;

    Inst Aragones Ciencias Salud, SAI Biomed & Biomat & Phenotyp Unit, Zaragoza 50009, Spain;

    Univ Santiago de Compostela, CIBERER, Grp Med Xenom, Santiago De Compostela 15782, Spain;

    Ctr Nacl Invest Cardiovasc Carlos III, Madrid 28029, Spain;

    Complexo Hosp Univ Santiago, SERGAS, Fdn Publ Gallega Med Xenom, Santiago De Compostela 15706, Spain;

    Univ Santiago de Compostela, CIBERER, Grp Med Xenom, Santiago De Compostela 15782, Spain|Complexo Hosp Univ Santiago, SERGAS, Fdn Publ Gallega Med Xenom, Santiago De Compostela 15706, Spain|King Abdulaziz Univ, Ctr Excellence Genom Med Res, Jeddah 21589, Saudi Arabia;

    Univ Zaragoza, Dept Bioquim & Biol Mol & Celular, E-50009 Zaragoza, Spain;

    Univ Zaragoza, Dept Bioquim & Biol Mol & Celular, E-50009 Zaragoza, Spain;

    Ctr Nacl Invest Cardiovasc Carlos III, Madrid 28029, Spain|CIBERES, C Melchor Fernandez Almagro 3, Madrid 28029, Spain|Univ Complutense Madrid, Madrid 28606, Spain;

    MRC, Mitochondrial Biol Unit, Hills Rd, Cambridge CB2 0XY, England;

    Ctr Nacl Invest Cardiovasc Carlos III, Madrid 28029, Spain;

    Ctr Nacl Invest Cardiovasc Carlos III, Madrid 28029, Spain;

    Ctr Nacl Invest Cardiovasc Carlos III, Madrid 28029, Spain|Univ Zaragoza, Dept Bioquim & Biol Mol & Celular, E-50009 Zaragoza, Spain;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号