Evidence of carbon monoxide-mediated phase advancement of the yeast metabolic cycle

Proc Natl Acad Sci U S A. 2009 Aug 25;106(34):14293-6. doi: 10.1073/pnas.0907786106. Epub 2009 Aug 11.

Abstract

Prototrophic strains of budding yeast exhibit robust metabolic cycles during continuous growth under nutrient-limiting conditions. Previous studies revealed periodic fluctuations of aminolevulinic acid, a precursor of heme, indicating that heme biosynthesis is temporally regulated during these metabolic cycles. The enzyme that catabolizes heme, heme oxygenase, was found to be expressed in a highly periodic manner at both the mRNA and protein level. Heme oxygenase generates the biological gas, carbon monoxide (CO), as a product of heme catabolism. It is shown that pulsed administration of CO induces a phase advancement into the oxidative, respiratory phase of the metabolic cycles. This CO-mediated phase advancement takes place only if the gas is administered during the temporal window when it is predicted to be generated. It is further shown that a yeast strain bearing a targeted deletion of the gene encoding heme oxygenase displays protracted metabolic cycles. These observations provide evidence that gaseous CO may function as a cellular signaling molecule that helps cue metabolic cycling.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Carbon Monoxide / metabolism*
  • Carbon Monoxide / pharmacology
  • Chromatography, Liquid
  • Heme / metabolism
  • Heme Oxygenase (Decyclizing) / genetics
  • Heme Oxygenase (Decyclizing) / metabolism
  • Mass Spectrometry
  • Metabolome / drug effects
  • Metabolome / physiology*
  • Metabolomics / methods*
  • Mutation
  • Oxidation-Reduction / drug effects
  • Oxygen / metabolism
  • Oxygen Consumption / drug effects
  • Peroxidases / genetics
  • Peroxidases / metabolism
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • Time Factors

Substances

  • Saccharomyces cerevisiae Proteins
  • Heme
  • Carbon Monoxide
  • HMX1 protein, S cerevisiae
  • Peroxidases
  • Heme Oxygenase (Decyclizing)
  • Oxygen