title: A metabolic strategy to enhance long-term survival by Phx1 through stationary phase-specific pyruvate decarboxylases in fission yeast.
abstract: In the fission yeast Schizosaccharomyces pombe, the stationary phase-specific transcription factor Phx1 contributes to long-term survival, stress tolerance, and meiosis. We identified Phx1-dependent genes through transcriptome analysis, and further analyzed those related with carbohydrate and thiamine metabolism, whose expression decreased in ∆phx1. Consistent with mRNA changes, the level of thiamine pyrophosphate (TPP) and TPP-utilizing pyruvate decarboxylase activity that converts pyruvate to acetaldehyde were also reduced in the mutant. Therefore, Phx1 appears to shift metabolic flux by diverting pyruvate from the TCA cycle and respiration to ethanol fermentation. Among the four predicted genes for pyruvate decarboxylase, only the Phx1-dependent genes (pdc201+ and pdc202+) contributed to long-term survival as judged by mutation and overexpression studies. These findings indicate that the Phx1-mediated long-term survival is achieved primarily through increasing the synthesis and activity of pyruvate decarboxylase. Consistent with this hypothesis, we observed that Phx1 curtailed respiration when cells entered stationary phase. Introduction of Δphx1 mutation compromised the long-lived phenotypes of Δpka1 and Δsck2 mutants that are devoid of pro-aging kinases of nutrient-signalling pathways, and of the Δpyp1 mutant with constitutively activated stress-responsive kinase Sty1. Therefore, achievement of long-term viability through both nutrient limitation and anti-stress response appears to be dependent on Phx1.
authors.affiliation: Laboratory of Molecular Microbiology, School of Biological Sciences, and Institute of Microbiology, Seoul National University, Seoul 151-747;
authors.forename: Ji-Yoon
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Laboratory of Molecular Microbiology, School of Biological Sciences, and Institute of Microbiology, Seoul National University, Seoul 151-747;
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Kim
authors.affiliation: University College London, Department of Genetics, Evolution and Environment, Darwin Building, Gower Street London WC1E 6BT, United Kingdom; Instituto de Bioquímica Vegetal y Fotosíntesis, CSIC-Universidad de Sevilla, Avenida Américo Vespucio, s/n, 41092 - Sevilla, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Lopez-Maury
authors.affiliation: University College London, Department of Genetics, Evolution and Environment, Darwin Building, Gower Street London WC1E 6BT, United Kingdom;
authors.forename: Jürg
authors.initials: J
authors.lastname: Bähler
authors.affiliation: Laboratory of Molecular Microbiology, School of Biological Sciences, and Institute of Microbiology, Seoul National University, Seoul 151-747;
authors.forename: Jung-Hye
authors.initials: JH
authors.lastname: Roe
mesh_terms: D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D015966:Gene Expression Regulation, Fungal / Q000502:physiology*; D008928:Mitochondria / Q000378:metabolism; D009154:Mutation; D010101:Oxygen Consumption / Q000502:physiology; D010802:Phylogeny; D011767:Pyruvate Decarboxylase / Q000235:genetics / Q000378:metabolism*; D017382:Reactive Oxygen Species; D012568:Schizosaccharomyces / Q000235:genetics / Q000378:metabolism*; D013312:Stress, Physiological; D013831:Thiamine; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D059467:Transcriptome
chemical_list: D005656:Fungal Proteins; D017382:Reactive Oxygen Species; D014157:Transcription Factors; D011767:Pyruvate Decarboxylase; D013831:Thiamine
references.citation: FEMS Microbiol Rev. 2000 Oct;24(4):507-29
references.pmid: 10978549
references.citation: Exp Cell Res. 1998 Dec 15;245(2):379-88
references.pmid: 9851879
references.citation: Aging Cell. 2005 Feb;4(1):41-52
references.pmid: 15659212
references.citation: Aging Cell. 2013 Aug;12(4):563-73
references.pmid: 23551936
references.citation: Nature. 2008 Jun 26;453(7199):1239-43
references.pmid: 18488015
references.citation: Aging Cell. 2006 Aug;5(4):345-57
references.pmid: 16822282
references.citation: Science. 2011 May 20;332(6032):930-6
references.pmid: 21511999
references.citation: Yeast. 1996 Dec;12(16):1607-33
references.pmid: 9123965
references.citation: Appl Environ Microbiol. 2003 Aug;69(8):4534-41
references.pmid: 12902239
references.citation: BMC Microbiol. 2012 May 30;12:86
references.pmid: 22646093
references.citation: FEMS Yeast Res. 2008 Jun;8(4):520-30
references.pmid: 18422613
references.citation: Microbiology (Reading). 2007 Nov;153(Pt 11):3667-3676
references.pmid: 17975074
references.citation: Nature. 2000 Nov 9;408(6809):239-47
references.pmid: 11089981
references.citation: J Biol Chem. 1995 Nov 24;270(47):28457-62
references.pmid: 7499352
references.citation: Nat Biotechnol. 2009 Jul;27(7):604-5
references.pmid: 19587661
references.citation: J Biol Chem. 2006 Jan 20;281(3):1345-51
references.pmid: 16299000
references.citation: Can J Microbiol. 2008 Sep;54(9):734-41
references.pmid: 18772936
references.citation: Nature. 2002 Jul 18;418(6895):344-8
references.pmid: 12124627
references.citation: J Biol Chem. 2008 Mar 21;283(12):7379-89
references.pmid: 18201975
references.citation: Cell. 2006 Jul 28;126(2):257-68
references.pmid: 16873059
references.citation: Aging (Albany NY). 2010 Apr;2(4):231-7
references.pmid: 20453258
references.citation: Nat Protoc. 2008;3(6):1101-8
references.pmid: 18546601
references.citation: Genome Biol. 2007;8(10):R217
references.pmid: 17927811
references.citation: Science. 2010 Apr 16;328(5976):321-6
references.pmid: 20395504
references.citation: J Mol Evol. 2008 Jan;66(1):36-49
references.pmid: 18043855
references.citation: Mol Biol Cell. 2003 Jan;14(1):214-29
references.pmid: 12529438
references.citation: Microbiol Mol Biol Rev. 2004 Jun;68(2):187-206
references.pmid: 15187181
references.citation: Nat Biotechnol. 2010 Jun;28(6):617-623
references.pmid: 20473289
references.citation: Mol Cell Biol. 2013 Mar;33(6):1244-53
references.pmid: 23319050
references.citation: Cell Metab. 2012 Jul 3;16(1):18-31
references.pmid: 22768836
references.citation: J Cell Sci. 1997 Oct;110 ( Pt 20):2557-66
references.pmid: 9372444
references.citation: BMC Genomics. 2003 Jul 10;4(1):27
references.pmid: 12854975
references.citation: Nat Genet. 2002 Sep;32(1):143-7
references.pmid: 12161753
references.citation: EMBO J. 2010 Mar 3;29(5):981-91
references.pmid: 20075862
references.citation: Ann N Y Acad Sci. 2010 Jun;1197:19-27
references.pmid: 20536828
references.citation: Biol Open. 2014 Feb 15;3(2):161-71
references.pmid: 24463365
references.citation: PLoS Genet. 2008 Jan;4(1):e13
references.pmid: 18225956
references.citation: Cell. 2007 Jun 29;129(7):1261-74
references.pmid: 17604717
references.citation: Curr Genet. 1991 Apr;19(4):249-54
references.pmid: 1868574
references.citation: Appl Environ Microbiol. 1990 Jan;56(1):281-7
references.pmid: 16348101
references.citation: Cell. 2012 Oct 26;151(3):671-83
references.pmid: 23101633