Interfering with Glycolysis Causes Sir2-dependent Hyper-recombination of Saccharomyces Cerevisiae Plasmids

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2009 Apr 25

PMID 19390637

Citations 6

Authors

Markus Ralser

Ute Zeidler

Hans Lehrach

Affiliations

Soon will be listed here.

Abstract

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a key metabolic regulator implicated in a variety of cellular processes. It functions as a glycolytic enzyme, a protein kinase, and a metabolic switch under oxidative stress. Its enzymatic inactivation causes a major shift in the primary carbohydrate flux. Furthermore, the protein is implicated in regulating transcription, ER-to-Golgi transport, and apoptosis. We found that Saccharomyces cerevisiae cells null for all GAPDH paralogues (Tdh1, Tdh2, and Tdh3) survived the counter-selection of a GAPDH-encoding plasmid when the NAD(+) metabolizing deacetylase Sir2 was overexpressed. This phenotype required a fully functional copy of SIR2 and resulted from hyper-recombination between S. cerevisiae plasmids. In the wild-type background, GAPDH overexpression increased the plasmid recombination rate in a growth-condition dependent manner. We conclude that GAPDH influences yeast episome stability via Sir2 and propose a model for the interplay of Sir2, GAPDH, and the glycolytic flux.

Citing Articles

The formation of hybrid complexes between isoenzymes of glyceraldehyde-3-phosphate dehydrogenase regulates its aggregation state, the glycolytic activity and sphingolipid status in Saccharomyces cerevisiae.

Randez-Gil F, Sanchez-Adria I, Estruch F, Prieto J Microb Biotechnol. 2019; 13(2):562-571.

PMID: 31743950 PMC: 7017825. DOI: 10.1111/1751-7915.13513.

Peroxynitrite-Mediated SIRT (Sirtuin)-1 Inactivation Contributes to Nicotine-Induced Arterial Stiffness in Mice.

Ding Y, Han Y, Lu Q, An J, Zhu H, Xie Z Arterioscler Thromb Vasc Biol. 2019; 39(7):1419-1431.

PMID: 31092012 PMC: 6613385. DOI: 10.1161/ATVBAHA.118.312346.

Yeast Tdh3 (glyceraldehyde 3-phosphate dehydrogenase) is a Sir2-interacting factor that regulates transcriptional silencing and rDNA recombination.

Ringel A, Ryznar R, Picariello H, Huang K, Lazarus A, Holmes S PLoS Genet. 2013; 9(10):e1003871.

PMID: 24146631 PMC: 3798266. DOI: 10.1371/journal.pgen.1003871.

Sirtuins as regulators of the yeast metabolic network.

Ralser M, Michel S, Breitenbach M Front Pharmacol. 2012; 3:32.

PMID: 22408620 PMC: 3296958. DOI: 10.3389/fphar.2012.00032.

Direct inhibition of tombusvirus plus-strand RNA synthesis by a dominant negative mutant of a host metabolic enzyme, glyceraldehyde-3-phosphate dehydrogenase, in yeast and plants.

Huang T, Nagy P J Virol. 2011; 85(17):9090-102.

PMID: 21697488 PMC: 3165801. DOI: 10.1128/JVI.00666-11.

References

Masri F, Comhair S, Koeck T, Xu W, Janocha A, Ghosh S . Abnormalities in nitric oxide and its derivatives in lung cancer. Am J Respir Crit Care Med. 2005; 172(5):597-605. PMC: 2718532. DOI: 10.1164/rccm.200411-1523OC. View

Dastoor Z, Dreyer J . Potential role of nuclear translocation of glyceraldehyde-3-phosphate dehydrogenase in apoptosis and oxidative stress. J Cell Sci. 2001; 114(Pt 9):1643-53. DOI: 10.1242/jcs.114.9.1643. View

Pollak N, Dolle C, Ziegler M . The power to reduce: pyridine nucleotides--small molecules with a multitude of functions. Biochem J. 2007; 402(2):205-18. PMC: 1798440. DOI: 10.1042/BJ20061638. View

Colussi C, Albertini M, Coppola S, Rovidati S, Galli F, Ghibelli L . H2O2-induced block of glycolysis as an active ADP-ribosylation reaction protecting cells from apoptosis. FASEB J. 2000; 14(14):2266-76. DOI: 10.1096/fj.00-0074com. View

McAlister L, Holland M . Differential expression of the three yeast glyceraldehyde-3-phosphate dehydrogenase genes. J Biol Chem. 1985; 260(28):15019-27. View

Grant C . Metabolic reconfiguration is a regulated response to oxidative stress. J Biol. 2008; 7(1):1. PMC: 2246036. DOI: 10.1186/jbiol63. View

Kaeberlein M, McVey M, Guarente L . The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms. Genes Dev. 1999; 13(19):2570-80. PMC: 317077. DOI: 10.1101/gad.13.19.2570. View

Gavin A, Bosche M, Krause R, Grandi P, Marzioch M, Bauer A . Functional organization of the yeast proteome by systematic analysis of protein complexes. Nature. 2002; 415(6868):141-7. DOI: 10.1038/415141a. View

Tanner K, Landry J, Sternglanz R, Denu J . Silent information regulator 2 family of NAD- dependent histone/protein deacetylases generates a unique product, 1-O-acetyl-ADP-ribose. Proc Natl Acad Sci U S A. 2000; 97(26):14178-82. PMC: 18891. DOI: 10.1073/pnas.250422697. View

10.

Verho R, Richard P, Jonson P, Sundqvist L, Londesborough J, Penttila M . Identification of the first fungal NADP-GAPDH from Kluyveromyces lactis. Biochemistry. 2002; 41(46):13833-8. DOI: 10.1021/bi0265325. View

11.

Wentzel P, Ejdesjo A, Eriksson U . Maternal diabetes in vivo and high glucose in vitro diminish GAPDH activity in rat embryos. Diabetes. 2003; 52(5):1222-8. DOI: 10.2337/diabetes.52.5.1222. View

12.

Bryk M, Banerjee M, Murphy M, Knudsen K, Garfinkel D, Curcio M . Transcriptional silencing of Ty1 elements in the RDN1 locus of yeast. Genes Dev. 1997; 11(2):255-69. DOI: 10.1101/gad.11.2.255. View

13.

Ralser M, Wamelink M, Kowald A, Gerisch B, Heeren G, Struys E . Dynamic rerouting of the carbohydrate flux is key to counteracting oxidative stress. J Biol. 2007; 6(4):10. PMC: 2373902. DOI: 10.1186/jbiol61. View

14.

Grunweller A, Ehrenhofer-Murray A . A novel yeast silencer. the 2mu origin of Saccharomyces cerevisiae has HST3-, MIG1- and SIR-dependent silencing activity. Genetics. 2002; 162(1):59-71. PMC: 1462261. DOI: 10.1093/genetics/162.1.59. View

15.

Ravichandran V, Seres T, Moriguchi T, Thomas J, JOHNSTON Jr R . S-thiolation of glyceraldehyde-3-phosphate dehydrogenase induced by the phagocytosis-associated respiratory burst in blood monocytes. J Biol Chem. 1994; 269(40):25010-5. View

16.

Verho R, Londesborough J, Penttila M, Richard P . Engineering redox cofactor regeneration for improved pentose fermentation in Saccharomyces cerevisiae. Appl Environ Microbiol. 2003; 69(10):5892-7. PMC: 201209. DOI: 10.1128/AEM.69.10.5892-5897.2003. View

17.

Holtgrefe S, Gohlke J, Starmann J, Druce S, Klocke S, Altmann B . Regulation of plant cytosolic glyceraldehyde 3-phosphate dehydrogenase isoforms by thiol modifications. Physiol Plant. 2008; 133(2):211-28. DOI: 10.1111/j.1399-3054.2008.01066.x. View

18.

Tisdale E, Artalejo C . A GAPDH mutant defective in Src-dependent tyrosine phosphorylation impedes Rab2-mediated events. Traffic. 2007; 8(6):733-41. PMC: 3775588. DOI: 10.1111/j.1600-0854.2007.00569.x. View

19.

Laschet J, Minier F, Kurcewicz I, Bureau M, Trottier S, Jeanneteau F . Glyceraldehyde-3-phosphate dehydrogenase is a GABAA receptor kinase linking glycolysis to neuronal inhibition. J Neurosci. 2004; 24(35):7614-22. PMC: 6729617. DOI: 10.1523/JNEUROSCI.0868-04.2004. View

20.

Shenton D, Grant C . Protein S-thiolation targets glycolysis and protein synthesis in response to oxidative stress in the yeast Saccharomyces cerevisiae. Biochem J. 2003; 374(Pt 2):513-9. PMC: 1223596. DOI: 10.1042/BJ20030414. View