title: The pentose phosphate pathway is a metabolic redox sensor and regulates transcription during the antioxidant response.
abstract: OBJECTIVE
  A shift in primary carbon metabolism is the fastest response to oxidative stress. Induced within seconds, it precedes transcriptional regulation, and produces reducing equivalents in form of NADPH within the pentose phosphate pathway (PPP).
  
  
  RESULTS
  Here, we provide evidence for a regulatory signaling function of this metabolic transition in yeast. Several PPP-deficiencies caused abnormal accumulation of intermediate metabolites during the stress response. These PPP-deficient strains had strong growth deficits on media containing oxidants, but we observed that part of their oxidant-phenotypes were not attributable to the production of NADPH equivalents. This pointed to a second, yet unknown role of the PPP in the antioxidant response. Comparing transcriptome profiles obtained by RNA sequencing, we found gene expression profiles that resembled oxidative conditions when PPP activity was increased. Vice versa, deletion of PPP enzymes disturbed and delayed mRNA and protein expression during the antioxidant response.
  
  
  METHODS
  Thus, the transient activation of the PPP is a metabolic signal required for balancing and timing gene expression upon an oxidative burst.
  
  
  CONCLUSIONS
  Consequently, dynamic rearrangements in central carbon metabolism seem to be of major importance for eukaryotic redox sensing, and represent a novel class of dynamic gene expression regulators.
authors.affiliation: Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors.forename: Antje
authors.initials: A
authors.lastname: Krüger
authors.forename: Nana-Maria
authors.initials: NM
authors.lastname: Grüning
authors.forename: Mirjam M C
authors.initials: MM
authors.lastname: Wamelink
authors.forename: Martin
authors.initials: M
authors.lastname: Kerick
authors.forename: Alexander
authors.initials: A
authors.lastname: Kirpy
authors.forename: Dimitri
authors.initials: D
authors.lastname: Parkhomchuk
authors.forename: Katharina
authors.initials: K
authors.lastname: Bluemlein
authors.forename: Michal-Ruth
authors.initials: MR
authors.lastname: Schweiger
authors.forename: Aleksey
authors.initials: A
authors.lastname: Soldatov
authors.forename: Hans
authors.initials: H
authors.lastname: Lehrach
authors.forename: Cornelis
authors.initials: C
authors.lastname: Jakobs
authors.forename: Markus
authors.initials: M
authors.lastname: Ralser
mesh_terms: D000975:Antioxidants / Q000378:metabolism*; D004579:Electron Transport; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006019:Glycolysis; D009154:Mutation; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction; D010427:Pentose Phosphate Pathway; D014158:Transcription, Genetic
chemical_list: D000975:Antioxidants; D009249:NADP