Ray Michael W, Chen WeiTing, Duan Chengzhe, Bravo Guadalupe, Krueger Kyle, Rosario Erica M, Jacob Alexis A, Lackner Laura L
Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208.
bioRxiv. 2025 Mar 26:2025.03.25.645216. doi: 10.1101/2025.03.25.645216.
Most eukaryotic cells maintain mitochondria in well-distributed, reticular networks. The size of the mitochondrial network and copy number of its genome scale with cell size. However, while the size scaling features of mitochondria and their genome are interrelated, the fitness consequences of this interdependence are not well understood. We exploit the asymmetric cell division of budding yeast to test the hypothesis that mitochondrial scaling with cell size impacts mitochondrial DNA (mtDNA) function. We find that the volume of mitochondria inherited by daughter cells affects the ability of cells to maintain functional mtDNA; daughter cells that inherit a significantly reduced volume of mitochondria have an increased frequency of losing respiratory competence. In cells with such mitochondrial inheritance defects, mtDNA integrity can be maintained by upregulating mtDNA copy number. Collectively, these data support a bet-hedging model whereby the faithful inheritance of an adequate volume of mitochondria ensures enough mtDNA copies are transmitted to daughter cells to counteract pre-existing and/or inevitable mtDNA mutations.
大多数真核细胞中的线粒体维持着分布良好的网状结构。线粒体网络的大小及其基因组的拷贝数随细胞大小而变化。然而，虽然线粒体及其基因组的大小缩放特征相互关联，但这种相互依存关系对适应性的影响尚未得到充分理解。我们利用芽殖酵母的不对称细胞分裂来检验线粒体随细胞大小缩放影响线粒体DNA（mtDNA）功能这一假设。我们发现子细胞继承的线粒体体积会影响细胞维持功能性mtDNA的能力；继承显著减少的线粒体体积的子细胞丧失呼吸能力的频率增加。在具有这种线粒体遗传缺陷的细胞中，通过上调mtDNA拷贝数可以维持mtDNA的完整性。总体而言，这些数据支持一种风险对冲模型，即足够体积的线粒体的忠实遗传可确保有足够的mtDNA拷贝传递给子细胞，以抵消预先存在的和/或不可避免的mtDNA突变。
