Evidence of carbon monoxide-mediated phase advancement of the yeast metabolic cycle.
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.
Tu
Benjamin P
BP
Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390-9038, USA. benjamin.tu@utsouthwestern.edu
McKnight
Steven L
SL
D015153:Blotting, Western; D002248:Carbon Monoxide / Q000378:metabolism* / Q000494:pharmacology; D002853:Chromatography, Liquid; D006418:Heme / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism; D013058:Mass Spectrometry; D055442:Metabolome / Q000187:drug effects / Q000502:physiology*; D055432:Metabolomics / Q000379:methods*; D009154:Mutation; D010084:Oxidation-Reduction / Q000187:drug effects; D010100:Oxygen / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D010544:Peroxidases / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
D029701:Saccharomyces cerevisiae Proteins; D006418:Heme; D002248:Carbon Monoxide; C478774:HMX1 protein, S cerevisiae; D010544:Peroxidases; D006419:Heme Oxygenase (Decyclizing); D010100:Oxygen
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