title: Reduced Glucose Sensation Can Increase the Fitness of Saccharomyces cerevisiae Lacking Mitochondrial DNA.
abstract: 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 proliferation of Saccharomyces cerevisiae cells lacking mtDNA and that 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 to cells lacking mtDNA by PKA inhibition, 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.
authors.affiliation: Department of Molecular Biology and Genetics, Koç University, Sarıyer, İstanbul, 34450, Turkey.
authors.forename: Emel
authors.initials: E
authors.lastname: Akdoğan
authors.affiliation: Department of Chemical and Biological Engineering, Koç University, Sarıyer, İstanbul, 34450, Turkey.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Tardu
authors.affiliation: Department of Molecular Biology and Genetics, Koç University, Sarıyer, İstanbul, 34450, Turkey.
authors.forename: Görkem
authors.initials: G
authors.lastname: Garipler
authors.affiliation: Department of Molecular Biology and Genetics, Koç University, Sarıyer, İstanbul, 34450, Turkey.
authors.forename: Gülkız
authors.initials: G
authors.lastname: Baytek
authors.affiliation: Department of Molecular Biology and Genetics, Koç University, Sarıyer, İstanbul, 34450, Turkey.|Department of Chemical and Biological Engineering, Koç University, Sarıyer, İstanbul, 34450, Turkey.
authors.forename: İ Halil
authors.initials: İH
authors.lastname: Kavakli
authors.affiliation: Department of Molecular Biology and Genetics, Koç University, Sarıyer, İstanbul, 34450, Turkey.
authors.forename: Cory D
authors.initials: CD
authors.lastname: Dunn
mesh_terms: D001120:Arginine / Q000737:chemistry; D049109:Cell Proliferation; D003470:Culture Media / Q000737:chemistry; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004249:DNA Damage; D004272:DNA, Mitochondrial / Q000235:genetics*; D005285:Fermentation; D017353:Gene Deletion; D005947:Glucose / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D009154:Mutation; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D003470:Culture Media; D004272:DNA, Mitochondrial; D033681:Mitochondrial Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D029701:Saccharomyces cerevisiae Proteins; C090857:TOM22 protein, S cerevisiae; C489039:TOM70 protein, S cerevisiae; D049452:Green Fluorescent Proteins; D001120:Arginine; D017868:Cyclic AMP-Dependent Protein Kinases; D005947:Glucose