title: Evidence of carbon monoxide-mediated phase advancement of the yeast metabolic cycle.
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.
authors.affiliation: Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390-9038, USA. benjamin.tu@utsouthwestern.edu
authors.forename: Benjamin P
authors.initials: BP
authors.lastname: Tu
authors.forename: Steven L
authors.initials: SL
authors.lastname: McKnight
mesh_terms: 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
chemical_list: D029701:Saccharomyces cerevisiae Proteins; D006418:Heme; D002248:Carbon Monoxide; C478774:HMX1 protein, S cerevisiae; D010544:Peroxidases; D006419:Heme Oxygenase (Decyclizing); D010100:Oxygen
references.citation: FASEB J. 1988 Jul;2(10):2557-68
references.pmid: 3290025
references.citation: Science. 1993 Jan 15;259(5093):381-4
references.pmid: 7678352
references.citation: Science. 2007 Dec 14;318(5857):1786-9
references.pmid: 18006707
references.citation: Annu Rev Biochem. 2002;71:307-31
references.pmid: 12045099
references.citation: Proc Natl Acad Sci U S A. 2007 Oct 23;104(43):16892-7
references.pmid: 17827275
references.citation: Antioxid Redox Signal. 2007 Dec;9(12):2139-55
references.pmid: 17854278
references.citation: Genes Dev. 2000 Dec 1;14(23):2950-61
references.pmid: 11114885
references.citation: Proc Natl Acad Sci U S A. 2007 Oct 23;104(43):16886-91
references.pmid: 17940006
references.citation: Antioxid Redox Signal. 2004 Oct;6(5):819-24
references.pmid: 15345141
references.citation: Mol Biol Cell. 1998 Dec;9(12):3273-97
references.pmid: 9843569
references.citation: Cell. 2001 Nov 30;107(5):567-78
references.pmid: 11733057
references.citation: Proc Natl Acad Sci U S A. 1985 Dec;82(23):7865-9
references.pmid: 3865203
references.citation: Proc Natl Acad Sci U S A. 1964 Jun;51:1244-51
references.pmid: 14215650
references.citation: Science. 2000 Dec 15;290(5499):2110-3
references.pmid: 11118138
references.citation: Cell. 2005 Jul 29;122(2):195-207
references.pmid: 16051145
references.citation: Nat Rev Mol Cell Biol. 2006 Sep;7(9):696-701
references.pmid: 16823381
references.citation: Biotechnol Bioeng. 1986 May;28(5):700-10
references.pmid: 18555381
references.citation: Biotechnol Bioeng. 1988 Aug 5;32(4):411-7
references.pmid: 18587737
references.citation: Arch Biochem Biophys. 1964 Oct;108:36-46
references.pmid: 14233914
references.citation: Mol Cell Biol. 2001 Mar;21(6):2098-106
references.pmid: 11238944
references.citation: J Biol Chem. 2003 Sep 19;278(38):36582-7
references.pmid: 12840010
references.citation: Yeast. 1998 Jul;14(10):953-61
references.pmid: 9717241
references.citation: Biochem Biophys Res Commun. 1964 Jun 1;16(2):174-81
references.pmid: 4224521
references.citation: Science. 2002 Dec 20;298(5602):2385-7
references.pmid: 12446832
references.citation: Neuron. 2001 Nov 20;32(4):657-71
references.pmid: 11719206
references.citation: Arch Mikrobiol. 1969;66(4):289-303
references.pmid: 5384632
references.citation: Science. 2001 Jan 19;291(5503):490-3
references.pmid: 11161204
references.citation: FEMS Microbiol Lett. 1992 Nov 1;77(1-3):261-7
references.pmid: 1334018
references.citation: Cold Spring Harb Symp Quant Biol. 2007;72:339-43
references.pmid: 18419291
references.citation: Nature. 2004 Jul 22;430(6998):467-71
references.pmid: 15269772
references.citation: Science. 2005 Nov 18;310(5751):1152-8
references.pmid: 16254148
references.citation: Cell. 2002 May 3;109(3):307-20
references.pmid: 12015981
references.citation: Proc Natl Acad Sci U S A. 2004 Feb 3;101(5):1200-5
references.pmid: 14734811