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研究揭示线粒体DNA异质性母婴传播机制
2019-10-06 18:36

西班牙卡洛斯三世国家心血管研究中心José Antonio Enríquez团队揭示线粒体DNA(mtDNA)异质性母婴传播的调控机制。2019年10月3日,该成果在线发表在国际知名学术期刊《细胞—代谢》上。

研究人员发现mtDNA异质性影响胚胎代谢、细胞适应性和诱导多能干细胞(iPSC)生成。因此,影响氧化磷酸化(OXPHOS)的遗传和药理干预会改变卵母细胞发育过程中和/或胚胎早期的mtDNA单倍型竞争。研究人员发现,异质行为可以落在从随机漂移到强烈选择的范围之内,具体取决于线粒体与核的相互作用和代谢因子。了解异质动态及其机理为基础生物学过程提供了新颖的知识,并增强了人们减轻影响mtDNA传播临床应用风险的能力。

据介绍,mtDNA在每个细胞中有多个副本,这些副本源自卵母细胞中的mtDNA的扩增。异质性(超过1种mtDNA变体),可能由于突变、父系mtDNA泄漏和旨在防止与mtDNA连锁的疾病遗传的新型医学技术所产生。异质表型的影响仍然知之甚少。小鼠研究导致mtDNA异质性母婴传播中随机漂移或单倍型选择的矛盾模型。

附:英文原文

Title: Regulation of Mother-to-Offspring Transmission of mtDNA Heteroplasmy

Author: Ana Latorre-Pellicer, Ana Victoria Lechuga-Vieco, Iain G. Johnston, Riikka H. Hmlinen, Juan Pellico, Raquel Justo-Méndez, Jose María Fernández-Toro, Cristina Clavería, Adela Guaras, Rocío Sierra, Jordi Llop, Miguel Torres, Luis Miguel Criado, Anu Suomalainen, Nick S. Jones, Jesús Ruíz-Cabello, José Antonio Enríquez

Issue&Volume: 3 October 2019

Abstract: mtDNA is present in multiple copies in each cell derived from the expansions of those in the oocyte. Heteroplasmy, more than one mtDNA variant, may be generated by mutagenesis, paternal mtDNA leakage, and novel medical technologies aiming to prevent inheritance of mtDNA-linked diseases. Heteroplasmy phenotypic impact remains poorly understood. Mouse studies led to contradictory models of random drift or haplotype selection for mother-to-offspring transmission of mtDNA heteroplasmy. Here, we show that mtDNA heteroplasmy affects embryo metabolism, cell fitness, and induced pluripotent stem cell (iPSC) generation. Thus, genetic and pharmacological interventions affecting oxidative phosphorylation (OXPHOS) modify competition among mtDNA haplotypes during oocyte development and/or at early embryonic stages. We show that heteroplasmy behavior can fall on a spectrum from random drift to strong selection, depending on mito-nuclear interactions and metabolic factors. Understanding heteroplasmy dynamics and its mechanisms provide novel knowledge of a fundamental biological process and enhance our ability to mitigate risks in clinical applications affecting mtDNA transmission.

DOI: 10.1016/j.cmet.2019.09.007

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(19)30510-8

Cell Metabolism:《细胞—代谢》,创刊于2005年。隶属于细胞出版社,最新IF:31.373
官方网址:https://www.cell.com/cell-metabolism/home
投稿链接:https://www.editorialmanager.com/cell-metabolism/default.aspx


本期文章:《细胞—代谢》:Online/在线发表

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