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Mitochondria are multifunctional organelles whose principal function is to produce chemical energy for cells. Instability of mitochondrial DNA (mtDNA) interrupts mitochondrial function, which in turn can beget a variety of diseases. We assayed several hundred strains of yeast for differences in the rates of mtDNA loss and performed a genome-wide association study to identify nuclear genes that influence mtDNA stability. We validated our findings by employing a collection of yeast strains, each bearing a knockout of a different gene. Our results show that genes involved in cell cycle regulation (WHI4) and proteins associated with oxidative phosphorylation (COQ11, YAT1) had significant effects on the rate of mtDNA loss. We were, however, surprised to find a number of genes involved in protein degradation to have an equal and sometimes greater effect on the efficacy of mitochondrial function. This suggests that the efficiency of mitochondrial function is strongly influenced by genes that are not directly associated with the mitochondria. By expanding our knowledge of factors that influence mitochondrial function, improved screening procedures for mitochondrial diseases can be developed, and new treatment avenues can potentially be explored.



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Identifying Genes Associated with Elevated Rates of Mitochondrial DNA Instability in a Yeast Model System