TWO nuclear genes, RTG1 and RTG2, which sense the functional state of yeast mitochondria, have been described recently. Yeast strains with null alleles of either of these two genes (△rtg1, △rtg2) cannot grow on acetate as the sole carbon source and are auxotrophic for glutamate and aspartate. We report here a series of metabolic experiments and enzyme activity measurements that were made in an attempt to determine the reason for the acetate-phenotype and the glutamate/aspartate auxotrophy. Decreases in the activities (~50%) in mitochondrial citrate synthase (CS1), acetyl-CoA synthetase, NAD isocitrate dehydrogenase, and pyruvate carboxylase were noted. When CS1 was overexpressed in the △rtg1 and △rtg2 mutants, these strains could grow on acetate but were still auxotrophic for glutamate/aspartate. We propose that, in the mutant strain, CS1 activity becomes limiting for efficient acetate utilization, but that other complex metabolic interactions are affected, limiting production of intermediates that would allow synthesis of glutamic and aspartic acids.
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