Integrity of the yeast mitochondrial genome, but not its distribution and inheritance, relies on mitochondrial fission and fusion
Integrity of the yeast mitochondrial genome, but not its distribution and inheritance, relies on mitochondrial fission and fusion
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DOI：
10.1073/pnas.1501737112
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发表时间：
2015-03-03
影响因子：
11.1
通讯作者：
Walter, Peter
中科院分区：
文献类型：
--
作者：
Osman, Christof;Noriega, Thomas R.;Walter, Peter
线粒体DNA （mtDNA）对线粒体和细胞功能至关重要。在酿酒酵母中，mtDNA被组织成称为类核的核蛋白结构，分布在整个线粒体网络中，并在细胞周期中忠实地遗传。细胞如何分布和遗传线粒体dna尚不完全清楚，尽管已经提出了线粒体裂变和融合的参与。我们开发了一种LacO-LacI系统来无创成像活细胞中的mtDNA动力学。利用该系统，我们发现类核在线粒体网络中是非随机分布的，并观察了线粒体dna遗传的时空事件。令人惊讶的是，缺乏线粒体融合和裂变的细胞正常分布和遗传mtDNA，这表明参与这些过程的其他途径。我们发现了这样一种机制，在那里我们观察到分裂无关，但f -肌动蛋白依赖，尖端的产生与mtDNA定位到新产生的尖端有关。尽管线粒体融合和裂变对于mtDNA的分布和遗传是必不可少的，但我们通过遗传学和下一代测序的结合表明，它们的缺失导致线粒体基因组的积累，这些基因组含有有害的结构变异，聚集在mtDNA复制的起源处，从而揭示了线粒体融合和裂变在维持线粒体基因组完整性方面的关键作用。
Mitochondrial DNA (mtDNA) is essential for mitochondrial and cellular function. In Saccharomyces cerevisiae, mtDNA is organized in nucleoprotein structures termed nucleoids, which are distributed throughout the mitochondrial network and are faithfully inherited during the cell cycle. How the cell distributes and inherits mtDNA is incompletely understood although an involvement of mitochondrial fission and fusion has been suggested. We developed a LacO-LacI system to noninvasively image mtDNA dynamics in living cells. Using this system, we found that nucleoids are nonrandomly spaced within the mitochondrial network and observed the spatiotemporal events involved in mtDNA inheritance. Surprisingly, cells deficient in mitochondrial fusion and fission distributed and inherited mtDNA normally, pointing to alternative pathways involved in these processes. We identified such a mechanism, where we observed fission-independent, but F-actin-dependent, tip generation that was linked to the positioning of mtDNA to the newly generated tip. Although mitochondrial fusion and fission were dispensable for mtDNA distribution and inheritance, we show through a combination of genetics and next-generation sequencing that their absence leads to an accumulation of mitochondrial genomes harboring deleterious structural variations that cluster at the origins of mtDNA replication, thus revealing crucial roles for mitochondrial fusion and fission in maintaining the integrity of the mitochondrial genome.