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Quality matters: how does mitochondrial network dynamics and quality control impact on mtDNA integrity?

机译:质量很重要:线粒体网络动力学和质量控制如何影响mtDNA完整性?

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摘要

Mammalian mtDNA encodes for 13 core proteins of oxidative phosphorylation. Mitochondrial DNA mutations and deletions cause severe myopathies and neuromuscular diseases. Thus, the integrity of mtDNA is pivotal for cell survival and health of the organism. We here discuss the possible impact of mitochondrial fusion and fission on mtDNA maintenance as well as positive and negative selection processes. Our focus is centred on the important question of how the quality of mtDNA nucleoids can be assured when selection and mitochondrial quality control works on functional and physiological phenotypes constituted by oxidative phosphorylation proteins. The organelle control theory suggests a link between phenotype and nucleoid genotype. This is discussed in the light of new results presented here showing that mitochondrial transcription factor Aucleoids are restricted in their intramitochondrial mobility and probably have a limited sphere of influence. Together with recent published work on mitochondrial and mtDNA heteroplasmy dynamics, these data suggest first, that single mitochondria might well be internally heterogeneous and second, that nucleoid genotypes might be linked to local phenotypes (although the link might often be leaky). We discuss how random or site-specific mitochondrial fission can isolate dysfunctional parts and enable their elimination by mitophagy, stressing the importance of fission in the process of mtDNA quality control. The role of fusion is more multifaceted and less understood in this context, but the mixing and equilibration of matrix content might be one of its important functions.
机译:哺乳动物的mtDNA编码13种氧化磷酸化的核心蛋白。线粒体DNA突变和缺失会导致严重的肌病和神经肌肉疾病。因此,mtDNA的完整性对于细胞存活和生物健康至关重要。我们在这里讨论线粒体融合和裂变对mtDNA维持以及阳性和阴性选择过程的可能影响。我们的重点集中在一个重要的问题上,即当选择和线粒体质量控制作用于由氧化磷酸化蛋白构成的功能和生理表型时,如何确保mtDNA核苷酸的质量。细胞器控制理论表明表型和核苷基因型之间的联系。将根据此处显示的新结果进行讨论,该结果表明线粒体转录因子A /核苷的线粒体内移动性受到限制,并且影响范围可能有限。这些数据与最近发表的有关线粒体和mtDNA异质动力学的最新研究结果一起表明,首先,单个线粒体很可能在内部具有异质性,其次,核苷的基因型可能与局部表型有关(尽管这种联系可能经常是泄漏的)。我们讨论随机或特定位置的线粒体裂变如何隔离功能异常的部分并通过线粒体消除它们,从而强调裂变在mtDNA质量控制过程中的重要性。在这种情况下,融合的作用更为多面且鲜为人知,但是基质含量的混合和平衡可能是其重要功能之一。

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