RT Journal Article SR Electronic T1 Reduced glucose sensation can increase the fitness of Saccharomyces cerevisiae lacking mitochondrial DNA JF bioRxiv FD Cold Spring Harbor Laboratory SP 024331 DO 10.1101/024331 A1 Emel Akdoğan A1 Mehmet Tardu A1 Görkem Garipler A1 Gülkiz Baytek A1 i. Halil Kavakli A1 Cory D. Dunn YR 2015 UL http://biorxiv.org/content/early/2015/08/10/024331.abstract AB Damage to the mitochondrial genome (mtDNA) can lead to diseases for which there are no clearly effective treatments. 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. We found that restricting glucose or otherwise reducing the activity of the protein kinase A (PKA) pathway can lead to improved fitness for Saccharomyces cerevisiae cells lacking mtDNA, and the transcriptional response to mtDNA loss is reduced in cells with diminished PKA activity. We have excluded many pathways and proteins from being individually responsible for the benefits provided by PKA inhibition to cells lacking mtDNA, and we found that robust import of mitochondrial polytopic membrane proteins may be required in order for cells without mtDNA to receive the full benefits of PKA reduction. Finally, we have discovered that the transcription of genes involved in arginine biosynthesis and aromatic amino acid catabolism is altered after mtDNA damage. Our results highlight the potential importance of nutrient detection and availability on the outcome of mitochondrial dysfunction.