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Regulation of Peroxisomal Fatty Acyl-CoA Oxidase in the Yeast

Saccharomyces cerevisiae

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 422))

Abstract

Peroxisomes are specialized organelles found in most eukaryote cells, where their major functions are in cellular respiration and fatty acid oxidation. Proliferation of this organelle, and induction of peroxisomal enzymes, is a phenomenon that occurs in diverse species, and is stimulated by a number of physiological and pharmacological stimuli. A large number of chemically diverse compounds, including hypolipidemic drugs and industrial plasticizers, have been shown to cause peroxisome proliferation and the induction of peroxisomal enzymes in rodents. Chronic exposure to these compounds produces hepatocellular carcinomas, however, the mechanism by which this tumorigenic event occurs is unknown. In the yeast Saccharomyces cerevisiae peroxisomes are induced when a fatty acid such as oleate is supplied as a carbon source in the growth medium. In addition, many peroxisomal enzymes are induced by growth on oleate; these include enzymes of the peroxisomal ß-oxidation cycle. This regulation occurs at the transcription level, and is controlled by specific trans-acting factors. The research in our laboratory has focused on the mechanisms involved in this regulation, and on the identification and characterization of the proteins involved. Our recent results, and current research directions are summarized.

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References

  1. C. de Duve and P. Baudhuin. Peroxisomes (microbodies and related particles). Physiol.Rev. 46: 323–357, (1966).

    Google Scholar 

  2. H. van den Bosch, R.B.H. Schutgens, R.J.A. Wanders and J.M. Tager. Biochemistry of peroxisomes. Annu.RevBjochem. 61: 157–197, (1992).

    Google Scholar 

  3. Lazarow, P.B. and Moser, H.W. Disorders of peroxisomal biogenesis. In: “The Metabolic Basis of Inherited Diseases”, edited by Scriver, C.R., Beaudet, A.L., Sly, W.S. and Valle, D. New York: McGraw-Hill Co., p. 1479–1509. (1989).

    Google Scholar 

  4. S. Goldfischer, C.L. Moore, A.B. Johnson, A.J. Spiro, M.P. Valsamis, H.K. Wisniewski, R.H. Ritch, W.T. Norton, I. Rapin and L.M. Gartner. Peroxisomal and mitochondrial defects in the cerebro-hepato-renal syndrome. Science 182: 62–64, (1973).

    Article  CAS  Google Scholar 

  5. E.A. Lock, A.M. Mitchell and C.R. Elcombe. Biochemical mechanisms of induction of hepatic peroxisome proliferation. Annu.RevPharmacol.Toxicol. 29: 145 - I63, (1989).

    Article  CAS  Google Scholar 

  6. C.E. Neat, M.S. Thomassen and H. Osmundsen. Induction of peroxisomal B-oxidation in rat liver by high fat diets. Biochem.J. 186: 369–371, (1980).

    CAS  Google Scholar 

  7. C.E. Neat, M.S. Thomassen and H. Osmundsen. Effects of high-fat diets on hepatic fatty acid oxidation in the rat. Isolation of rat liver peroxisomes by vertical-rotor, iso-osmotic, Percoll gradient. Biochem.J. 196: 149–159, (1981).

    CAS  Google Scholar 

  8. H. Ishii, S. Horie and T. Suga. Physiological role of peroxisomal 0-oxidation in liver of fasted rats. J.Biochem. 87: 1855–1858, (1980).

    CAS  Google Scholar 

  9. J.K. Reddy and N.D. Lalwani. Carcinogenesis by hepatic peroxisome proliferators: Evaluation of the risk of hypolipidemic drugs and industrial plasticizers to humans. Crit.Rev.Toxicol. 12: 1–58, (1983).

    Article  CAS  Google Scholar 

  10. M.S. Rao and J.K. Reddy. Peroxisome proliferation and hepatocarcinogenesis. Carcinogenesis 8: 631–636, (1987).

    Article  CAS  Google Scholar 

  11. Popp, J.A. and Cattley, R.C. Peroxisome proliferators as initiators and promoters of rodent hepatocarcinogenesis. In: “Peroxisomes: Biology and importance in toxicology and medicine”, edited by Gibson, G. and Lake, B. London: Taylor and Francis, p. 653–665. (1993).

    Google Scholar 

  12. J.K. Reddy, N.D. Lalwani, M.K. Reddy and S.A. Qureshi. Excessive accumulation of autofluorescent lipofuscin in the liver during hepatocarcinogenesis by methyl clofenepate and other hypolipidemic peroxisome proliferators. Cancer Res. 42: 259–266, (1982).

    CAS  Google Scholar 

  13. J.K. Reddy and M.S. Rao. Oxidative DNA damage caused by persistent peroxisome proliferation: its role in hepatocarcinogenesis. Mutation Research 214: 63–68, (1989).

    Article  CAS  Google Scholar 

  14. M.S. Rao and J.K. Reddy. An overview of peroxisome proliferator-induced hepatocarcinogenesis. Environ.Health Perspect. 93: 205–209, (1991).

    Article  CAS  Google Scholar 

  15. R.C. Cattley and J.A. Popp. Differences between the promoting activities of the peroxisome proliferator WY-14,643 and phenobarbital in rat liver. Cancer Res. 49: 3246–3251, (1989).

    CAS  Google Scholar 

  16. Issemann and S. Green. Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators. Nature 347: 645–6650, (1990).

    Article  CAS  Google Scholar 

  17. S.A. Kliewer, B.M. Forman, B. Blumberg, E.S. Ong, U. Borgmeyer, D.J. Mangelsdorf, K. Umesong and R.M. Evans. Differential expression and activation of a family of murine peroxisome proliferator-activated receptors. Proc.Natl.Acad.Sci.USA 91: 7355–7359, (1996).

    Article  Google Scholar 

  18. C. Dreyer, G. Krey, H. Keller, F. Givel, G. Helftenbein and W. Wahli. Control of the peroxisomal 0-oxidation pathway by a novel family of nuclear hormone receptors. Cell 68: 879–887, (1992).

    Article  CAS  Google Scholar 

  19. M. Gottlicher, E. Widmark, Q. Li and J-A. Gustafsson. Fatty acids activate a chimera of the clofibrate acid-activated receptor and the glucocorticoid receptor. Proc.Natl.Acad.Sci. USA 89: 4653–4657, (1992).

    Article  CAS  Google Scholar 

  20. J.D. Tugwood, L Issemann, R.G. Anderson, K.R. Bundell, W.L. McPheat and S. Green. The mouse peroxisome proliferator activated receptor recognizes a response element in the 5’ flanking sequence of the rat acyl CoA oxidase gene. EMBO J. 11: 433–439, (1992).

    CAS  Google Scholar 

  21. S.A. Kliewer, K. Umesono, D.J. Noonan, R.A. Heyman and R.M. Evans. Convergence of 9-cis retinoic acid and peroxisome proliferator signalling pathways through heterodimer formation of their receptors. Nature 358: 771–774, (1992).

    Article  CAS  Google Scholar 

  22. M. Veenhuis, M. Mateblowski, W.H. Kunau and W. Harder. Proliferation of microbodies in Saccharomyces cerevisiae. Yeast 3: 77–84, (1987).

    Article  CAS  Google Scholar 

  23. A. Dmochowska, D. Dignard, R. Maleszka and D.Y. Thomas. Structure and transcriptional control of the Saccharomyces cerevisiae PDX/ gene encoding acyl-coenzyme A oxidase. Gene 88: 247–252, (1990).

    Article  CAS  Google Scholar 

  24. T.W. Wang, A.S. Lewin and G.M. Small. A negative regulating element controlling transcription of the gene encoding acyl-CoA oxidase in Saccharomyces cerevisiae. Nucleic Acids Res. 20: 3495–3500, (1992).

    Article  CAS  Google Scholar 

  25. T. Wang, Y. Luo and G.M. Small. The PDX1 gene encoding peroxisomal acyl-CoA oxidase in Saccharomyces cerevisiae is under the control of multiple regulatory elements. J.Biol.Chem. 269: 24480–24485, (1994).

    CAS  Google Scholar 

  26. A.W.C. Einerhand, T.M. Voorn-Brouwer, R. Erdmann, W-H. Kunau and H.F. Tabak. Regulation of transcription of the gene coding for peroxisomal 3-oxoacyl-CoA thiolase of Saccharomyces cerevisiae. Eur.J. Biochem. 200: 113–122, (1991).

    Article  CAS  Google Scholar 

  27. A.W.0 Einerhand, W.T. Kos, B. Distel and H.F. Tabak. Characterization of a transcriptional control element involved in proliferation of peroxisomes in yeast in response to oleate. Eur:J.Biochem. 314: 323–331, (1993).

    Article  Google Scholar 

  28. W. Kos, A.J. Kat, S. van Wilpe and H.F. Tabak. Expression of genes encoding peroxisomal proteins in Saccharomyces cerevisiae is regulated by different circuits of transcriptional control. Biochim.Biophvs.Acta 1264: 79–86, (1995).

    Article  Google Scholar 

  29. Y. Luo, I.V. Karpichev, R.A. Kohanski and G.M. Small. Purification, identification and properties of a Saccharomyces cerevisiae oleate-activated upstream activating sequence-binding protein that is involved in the activation of PDX1. J.Biol.Chem. 271: 12068–12075, (1996).

    Article  CAS  Google Scholar 

  30. J.W. Zhang, Y. Han and P.B. Lazarow. Novel peroxisome clustering mutants and peroxisome biogenesis mutants of Saccharomyces cerevisiae. J.Cell Biol. 123: 1133–1147, (1993).

    Article  CAS  Google Scholar 

  31. R. Erdmann, M. Veenhuis, D. Mertens and W-I-I. Kunau. Isolation of peroxisome-deficient mutants of Saccharomyces cerevisiae. Proc.Natl.Acad.Sci. USA 86: 5419–5423, (1989).

    Article  CAS  Google Scholar 

  32. R.J. Reece and M. Ptashne. Determinants of binding-site specificity among yeast C6 zinc cluster proteins. Science 261: 909–911, (1993).

    Article  CAS  Google Scholar 

  33. W.H. Landschulz, P.F. Johnson and S.L. McKnight. The leucine zipper: a hypothetical structure common to a new class of DNA binding proteins. Science 240: 1759–1764, (1988).

    Article  CAS  Google Scholar 

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© 1997 Springer Science+Business Media New York

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Small, G.M., Karpichev, I.V., Luo, Y. (1997). Regulation of Peroxisomal Fatty Acyl-CoA Oxidase in the Yeast. In: Dietary Fat and Cancer. Advances in Experimental Medicine and Biology, vol 422. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-2670-1_13

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  • DOI: https://doi.org/10.1007/978-1-4757-2670-1_13

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4419-3282-2

  • Online ISBN: 978-1-4757-2670-1

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