Azaltılmış Protein Kinaz A (PKA) aktivitesi, mtDNA'sı olmayan Saccharomyces cerevisiae hücrelerinde büyüme kusurlarını ortadan kaldırabilir

Damage to the mitochondrial genome (mtDNA) severely affects the cell and causes disease. Mutations to mtDNA also accumulate throughout the lifespan of many organisms and may be a proximal cause of aging. There is no effective treatment for ailments caused by mtDNA mutation. Since mitochondrial function and biogenesis are controlled by the nutrient environment of the cell, it is possible that perturbation of conserved, nutrient-sensing pathways may successfully treat mitochondrial disease. Experiments using the tractable eukaryote Saccharomyces cerevisiae allow us to investigate the connection between nutrient-sensing and mitochondrial function. The main focus of my thesis is on the protein kinase A (PKA) pathway, which controls S. cerevisiae behavior according to glucose availability. We found that reduced PKA signaling leads to improved fitness after mtDNA loss. Our findings support the idea that glucose sensation is harmful for cells lacking the mitochondrial genome, however these effects are heavily dependent upon yeast genetic background. Interestingly, robust import of mitochondrial polytopic membrane proteins may be required in order for cells with no mtDNA to receive the full benefits of PKA reduction.