Publication: Reduced glucose sensation can increase the fitness of saccharomyces cerevisiae Lacking mitochondrial DNA
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Program
KU-Authors
KU Authors
Co-Authors
Akdoğan, E.
Tardu, M.
Garipler, G.
Baytek, G.
Advisor
Publication Date
2016
Language
English
Type
Journal Article
Journal Title
Journal ISSN
Volume Title
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.
Description
Source:
PLOS One
Publisher:
Public Library of Science
Keywords:
Subject
Science and technology