Attenuation of transcriptional and signaling responses limits viability of ρ(0)Saccharomyces cerevisiae during periods of glucose deprivation.

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  • Author(s): Friis RMN;Friis RMN; Schultz MC; Schultz MC
  • Source:
    Biochimica et biophysica acta [Biochim Biophys Acta] 2016 Nov; Vol. 1860 (11 Pt A), pp. 2563-2575. Date of Electronic Publication: 2016 Jul 29.
  • Publication Type:
    Journal Article; Research Support, Non-U.S. Gov't
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Elsevier Pub. Co Country of Publication: Netherlands NLM ID: 0217513 Publication Model: Print-Electronic Cited Medium: Print ISSN: 0006-3002 (Print) Linking ISSN: 00063002 NLM ISO Abbreviation: Biochim Biophys Acta Subsets: MEDLINE
    • Publication Information:
      Original Publication: Amsterdam : Elsevier Pub. Co.
    • Subject Terms:
      Gene Expression Regulation, Fungal*; DNA, Mitochondrial/*genetics ; Glucose/*deficiency ; Saccharomyces cerevisiae/*metabolism; Cell Division ; Glucose/metabolism ; Glycogen Synthase Kinase 3 beta/genetics ; Glycogen Synthase Kinase 3 beta/metabolism ; Intracellular Signaling Peptides and Proteins/genetics ; Intracellular Signaling Peptides and Proteins/metabolism ; Protein Kinases/genetics ; Protein Kinases/metabolism ; Protein Serine-Threonine Kinases/genetics ; Protein Serine-Threonine Kinases/metabolism ; Saccharomyces cerevisiae/cytology ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae Proteins/genetics ; Saccharomyces cerevisiae Proteins/metabolism ; Signal Transduction ; Transcriptional Activation
    • Abstract:
      Background: The maintenance of viability during periods when a glycolytic carbon source is limited (or absent) is a major obstacle for cells whose mitochondrial DNA (mtDNA) has been damaged or lost.
      Methods: We utilized genome wide transcriptional profiling and in gel mobility analyses to examine the transcriptional response and characterize defects in the phosphorylation dependent signaling events that occur during acute glucose starvation in ρ(0) cells that lack mtDNA. Genetic and pharmacological interventions were employed to clarify the contribution of nutrient responsive kinases to regulation of the transcription factors that displayed abnormal phosphoregulation in ρ(0) cells.
      Results: The transcriptional response to glucose deprivation is dampened but not blocked in ρ(0) cells. Genes regulated by the transcription factors Mig1, Msn2, Gat1, and Ume6 were noticeably affected and phosphorylation of these factors in response to nutrient depletion is abnormal in ρ(0) cells. Regulation of the nutrient responsive kinases PKA and Snf1 remains normal in ρ(0) cells. The phosphorylation defect results from ATP depletion and loss of the activity of kinases including GSK3β, Rim15, and Yak1. Interventions which rescue phosphoregulation of transcription factors bolster maintenance of viability in ρ(0) cells during subsequent glucose deprivation.
      Conclusions: A subset of nutrient responsive kinases is especially sensitive to ATP levels and their misregulation may underlie regulatory defects presented by ρ(0) cells.
      General Significance: Abnormal regulation of mitochondrial function is implicated in numerous human disorders. This work illustrates that some signaling pathways are more sensitive than others to metabolic defects caused by mitochondrial dysfunction.
      (Copyright © 2016 Elsevier B.V. All rights reserved.)
    • Comments:
      Erratum in: Biochim Biophys Acta. 2017 Jan;1861(1 Pt A):3498-3499. (PMID: 27693127)
    • Contributed Indexing:
      Keywords: Glucose; Mitochondria; Signaling; Transcription; Viability; Yeast.
    • Accession Number:
      0 (DNA, Mitochondrial)
      0 (Intracellular Signaling Peptides and Proteins)
      0 (Saccharomyces cerevisiae Proteins)
      EC 2.7.- (Protein Kinases)
      EC 2.7.1.- (Rim15 protein, S cerevisiae)
      EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
      EC 2.7.11.1 (Protein Serine-Threonine Kinases)
      EC 2.7.11.1 (YAK1 protein, S cerevisiae)
      IY9XDZ35W2 (Glucose)
    • Publication Date:
      Date Created: 20160802 Date Completed: 20170626 Latest Revision: 20211204
    • Publication Date:
      20231215
    • Accession Number:
      10.1016/j.bbagen.2016.07.029
    • Accession Number:
      27478089