While yeast cells lacking mitochondrial DNA cannot perform oxidative phosphorylation (respiration), they remain viable by relying on aerobic glycolysis (fermentation). In contrast, most eukaryotic cells retain, and even require, respiration. Thus we were interested in determining whether S. cerevisiae cells that retain respiratory competence throughout their replicative life span (RLS) also exhibit a mutator phenotype. The frequency at which functional mitochondria are successfully segregated during cell division varies widely between strains of S. cerevisiae; alleles in over 100 genes can affect mitochondrial DNA transmission frequency [13]–[15]. Therefore, in this study we sought to use a strain in which respiration competence was faithfully transmitted with increasing replicative age.