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

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16 Scopus citations


Prototrophic strains of budding yeast exhibit robust metabolic cycles during continuous growth under nutrient-limiting conditions. Previous studies revealed periodic fluctuations of aminole-vulinic 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.

Original languageEnglish (US)
Pages (from-to)14293-14296
Number of pages4
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number34
StatePublished - Aug 25 2009


  • Biological gas
  • Circadian
  • Heme
  • Metabolic state
  • Oscillation

ASJC Scopus subject areas

  • General


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