Although mitochondrial DNA (mtDNA) is prone to accumulate mutations and lacks conventional DNA repair mechanisms, deleterious mutations are exceedingly rare. How the transmission of detrimental mtDNA mutations is restricted through the maternal lineage is debated. Here, we demonstrate that mitochondrial fission, together with the lack of mtDNA replication, segregate mtDNA into individual organelles in the Drosophila early germarium. After mtDNA segregation, mtDNA transcription begins, which activates respiration. Mitochondria harboring wild-type genomes have functional electron transport chains and propagate more vigorously than mitochondria containing deleterious mutations in hetreoplasmic cells. Therefore, mtDNA expression acts as a stress test for the integrity of mitochondrial genomes and sets the stage for replication competition. Our observations support selective inheritance at the organelle level through a series of developmentally orchestrated mitochondrial processes. We also show that the Balbiani body has a minor role in mtDNA selective inheritance by supplying healthy mitochondria to the pole plasm. These two mechanisms may act synergistically to secure the transmission of functional mtDNA through Drosophila oogenesis.

中文翻译：

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线粒体 DNA 分离和复制限制有害突变的传播

尽管线粒体 DNA (mtDNA) 很容易积累突变并且缺乏传统的 DNA 修复机制，但有害突变极其罕见。如何限制有害 mtDNA 突变通过母系的传播仍存在争议。在这里，我们证明线粒体裂变以及线粒体 DNA 复制的缺乏，将线粒体 DNA 分离到果蝇早期胚芽中的单个细胞器中。mtDNA 分离后，mtDNA 转录开始，从而激活呼吸。含有野生型基因组的线粒体具有功能性电子传递链，并且比异质细胞中含有有害突变的线粒体更活跃地繁殖。因此，线粒体DNA表达可以作为线粒体基因组完整性的压力测试，并为复制竞争奠定基础。我们的观察结果支持通过一系列发育精心安排的线粒体过程在细胞器水平上进行选择性遗传。我们还表明，巴尔比亚尼体通过向极质提供健康的线粒体，在线粒体 DNA 选择性遗传中发挥次要作用。这两种机制可能协同作用，以确保功能性线粒体DNA通过果蝇卵子发生的传递。