Mitochondrial DNA (mtDNA) is present in multiple copies within cells and is required for mitochondrial ATP generation. Even within individual cells, mtDNA copies can differ in their sequence, a state known as heteroplasmy. The principles underlying dynamic changes in the degree of heteroplasmy remain incompletely understood, due to the inability to monitor this phenomenon in real time. Here, we employ mtDNA-based fluorescent markers, microfluidics, and automated cell tracking, to follow mtDNA variants in live heteroplasmic yeast populations at the single-cell level. This approach, in combination with direct mtDNA tracking and data-driven mathematical modeling reveals asymmetric partitioning of mtDNA copies during cell division, as well as limited mitochondrial fusion and fission frequencies, as critical driving forces for mtDNA variant segregation. Given that our approach also facilitates assessment of segregation between intact and mutant mtDNA, we anticipate that it will be instrumental in elucidating the mechanisms underlying the purifying selection of mtDNA.

中文翻译：

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在单细胞水平实时评估线粒体 DNA 异质性动力学。


线粒体 DNA （mtDNA） 在细胞内以多个拷贝的形式存在，是线粒体 ATP 生成所必需的。即使在单个细胞中，mtDNA 拷贝的序列也可能不同，这种状态称为异质性。由于无法实时监测这种现象，异质性程度动态变化的基本原理仍不完全清楚。在这里，我们采用基于 mtDNA 的荧光标记、微流体和自动细胞追踪，在单细胞水平上跟踪活异质酵母种群中的 mtDNA 变体。这种方法与直接 mtDNA 追踪和数据驱动的数学建模相结合，揭示了细胞分裂过程中 mtDNA 拷贝的不对称分配，以及有限的线粒体融合和裂变频率，是 mtDNA 变体分离的关键驱动力。鉴于我们的方法还有助于评估完整和突变 mtDNA 之间的分离，我们预计它将有助于阐明 mtDNA 纯化选择的潜在机制。