The Volume of Mitochondria Inherited Impacts mtDNA Homeostasis in Budding Yeast

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.