Reduced Glucose Sensation Can Increase the Fitness of Saccharomyces cerevisiae Lacking Mitochondrial DNA

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 succes...

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Bibliographic Details
Published in:PloS one 2016-01, Vol.11 (1), p.e0146511
Main Authors: Akdoğan, Emel, Tardu, Mehmet, Garipler, Görkem, Baytek, Gülkız, Kavakli, İ Halil, Dunn, Cory D
Format: Article
Language:English
Subjects:
Amino acids
Analysis
Arginine
Arginine - chemistry
Bioengineering
Biosynthesis
Catabolism
Cell Proliferation
Culture Media - chemistry
Cyclic AMP-Dependent Protein Kinases - metabolism
Cytosol - metabolism
Damage detection
Deoxyribonucleic acid
DNA
DNA Damage
DNA, Mitochondrial - genetics
Drug resistance
Fermentation
Fitness
Gene Deletion
Gene expression
Genetic aspects
Genetic engineering
Genomes
Glucose
Glucose - metabolism
Green Fluorescent Proteins - metabolism
Iron
Kinases
Membrane proteins
Microscopy, Fluorescence
Mitochondria
Mitochondria - metabolism
Mitochondrial DNA
Mitochondrial Membrane Transport Proteins - metabolism
Mitochondrial Precursor Protein Import Complex Proteins
Molecular biology
Mutation
Nutrient availability
Nutrients
Phosphorylation
Physiological aspects
Plasmids - metabolism
Protein kinase A
Proteins
Saccharomyces cerevisiae
Saccharomyces cerevisiae - genetics
Saccharomyces cerevisiae Proteins - metabolism
Signal Transduction
Transcription
Yeast
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0146511