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Cristae-dependent quality control of the mitochondrial genome
Science Advances ( IF 11.7 ) Pub Date : 2021-09-01 , DOI: 10.1126/sciadv.abi8886
Christopher Jakubke 1, 2 , Rodaria Roussou 1, 2 , Andreas Maiser 1 , Christina Schug 3 , Felix Thoma 1, 2 , David Bunk 1 , David Hörl 1 , Heinrich Leonhardt 1 , Peter Walter 4, 5 , Till Klecker 3 , Christof Osman 1
Affiliation  

Mitochondrial genomes (mtDNA) encode essential subunits of the mitochondrial respiratory chain. Mutations in mtDNA can cause a shortage in cellular energy supply, which can lead to numerous mitochondrial diseases. How cells secure mtDNA integrity over generations has remained unanswered. Here, we show that the single-celled yeast Saccharomyces cerevisiae can intracellularly distinguish between functional and defective mtDNA and promote generation of daughter cells with increasingly healthy mtDNA content. Purifying selection for functional mtDNA occurs in a continuous mitochondrial network and does not require mitochondrial fission but necessitates stable mitochondrial subdomains that depend on intact cristae morphology. Our findings support a model in which cristae-dependent proximity between mtDNA and the proteins it encodes creates a spatial “sphere of influence,” which links a lack of functional fitness to clearance of defective mtDNA.

中文翻译:

线粒体基因组的嵴依赖性质量控制

线粒体基因组 (mtDNA) 编码线粒体呼吸链的基本亚基。mtDNA 的突变会导致细胞能量供应短缺,从而导致许多线粒体疾病。细胞如何在几代人中确保 mtDNA 的完整性仍未得到解答。在这里,我们展示了单细胞酵母Saccharomyces cerevisiae可以在细胞内区分功能性和有缺陷的 mtDNA,并促进产生具有越来越健康的 mtDNA 含量的子细胞。功能性 mtDNA 的纯化选择发生在连续的线粒体网络中,不需要线粒体裂变,但需要依赖于完整嵴形态的稳定线粒体亚结构域。我们的研究结果支持一个模型,其中 mtDNA 与其编码的蛋白质之间的嵴依赖性接近产生了一个空间“影响范围”,它将功能适应性的缺乏与缺陷 mtDNA 的清除联系起来。
更新日期:2021-09-01
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