{Reference Type}: Journal Article
{Title}: Slow Growth and Increased Spontaneous Mutation Frequency in Respiratory Deficient afo1- Yeast Suppressed by a Dominant Mutation in ATP3.
{Author}: Li J;Rinnerthaler M;Hartl J;Weber M;Karl T;Breitenbach-Koller H;Mülleder M;Vowinckel J;Marx H;Sauer M;Mattanovich D;Ata Ö;De S;Greslehner GP;Geltinger F;Burhans B;Grant C;Doronina V;Ralser M;Streubel MK;Grabner C;Jarolim S;Moßhammer C;Gourlay CW;Hasek J;Cullen PJ;Liti G;Ralser M;Breitenbach M;
{Journal}: G3 (Bethesda)
{Volume}: 10
{Issue}: 12
{Year}: 12 2020 3
{Factor}: 3.542
{DOI}: 10.1534/g3.120.401537
{Abstract}: A yeast deletion mutation in the nuclear-encoded gene, AFO1, which codes for a mitochondrial ribosomal protein, led to slow growth on glucose, the inability to grow on glycerol or ethanol, and loss of mitochondrial DNA and respiration. We noticed that afo1- yeast readily obtains secondary mutations that suppress aspects of this phenotype, including its growth defect. We characterized and identified a dominant missense suppressor mutation in the ATP3 gene. Comparing isogenic slowly growing rho-zero and rapidly growing suppressed afo1- strains under carefully controlled fermentation conditions showed that energy charge was not significantly different between strains and was not causal for the observed growth properties. Surprisingly, in a wild-type background, the dominant suppressor allele of ATP3 still allowed respiratory growth but increased the petite frequency. Similarly, a slow-growing respiratory deficient afo1- strain displayed an about twofold increase in spontaneous frequency of point mutations (comparable to the rho-zero strain) while the suppressed strain showed mutation frequency comparable to the respiratory-competent WT strain. We conclude, that phenotypes that result from afo1- are mostly explained by rapidly emerging mutations that compensate for the slow growth that typically follows respiratory deficiency.