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. 1988 Nov;8(11):4773–4779. doi: 10.1128/mcb.8.11.4773

Inositol regulates phosphatidylglycerolphosphate synthase expression in Saccharomyces cerevisiae.

M L Greenberg 1, S Hubbell 1, C Lam 1
PMCID: PMC365569  PMID: 2850468

Abstract

The enzyme phosphatidylglycerolphosphate synthase (PGPS; CDPdiacylglycerol-glycerol-3-phosphate 3-phosphatidyltransferase; EC 2.7.8.5) catalyzes the committed step in the synthesis of cardiolipin, a phospholipid found predominantly in the mitochondrial inner membrane. To determine whether PGPS is regulated by cross-pathway control, we analyzed PGPS expression under conditions in which the regulation of general phospholipid synthesis could be examined. The addition of inositol resulted in a three- to fivefold reduction in PGPS expression in wild-type cells in the presence or absence of exogenous choline. The reduction in enzyme activity in response to inositol was seen in minutes, suggesting that inactivation or degradation of the enzyme plays an important role in inositol-mediated repression of PGPS. In cho2 and opi3 mutants, which are blocked in phosphatidylcholine synthesis, inositol-mediated repression of PGPS did not occur unless choline was added to the media. Three previously identified genes that regulate general phospholipid synthesis, INO2, INO4, and OP11, did not affect PGPS expression. Thus, ino2 and ino4 mutants, which are unable to derepress biosynthetic enzymes involved in general phospholipid synthesis, expressed wild-type levels of PGPS activity under derepressing conditions. PGPS expression in the opi1 mutant, which exhibits constitutive synthesis of general phospholipid biosynthetic enzymes, was fully repressed in the presence of inositol and partially repressed even in the absence of inositol. These results demonstrate for the first time that an enzymatic step in cardiolipin synthesis is coordinately controlled with general phospholipid synthesis but that this control is not mediated by the same genetic regulatory circuit.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bailis A. M., Poole M. A., Carman G. M., Henry S. A. The membrane-associated enzyme phosphatidylserine synthase is regulated at the level of mRNA abundance. Mol Cell Biol. 1987 Jan;7(1):167–176. doi: 10.1128/mcb.7.1.167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1006/abio.1976.9999. [DOI] [PubMed] [Google Scholar]
  3. Carman G. M., Belunis C. J. Phosphatidylglycerophosphate synthase activity in Saccharomyces cerevisiae. Can J Microbiol. 1983 Oct;29(10):1452–1457. doi: 10.1139/m83-222. [DOI] [PubMed] [Google Scholar]
  4. Carson M. A., Emala M., Hogsten P., Waechter C. J. Coordinate regulation of phosphatidylserine decarboxylase activity and phospholipid N-methylation in yeast. J Biol Chem. 1984 May 25;259(10):6267–6273. [PubMed] [Google Scholar]
  5. Cobon G. S., Crowfoot P. D., Linnane A. W. Biogenesis of mitchondria. Phospholipid synthesis in vitro by yeast mitochondrial and microsomal fractions. Biochem J. 1974 Nov;144(2):265–275. doi: 10.1042/bj1440265. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Culbertson M. R., Donahue T. F., Henry S. A. Control of inositol biosynthesis in Saccharomyces cerevisiae: properties of a repressible enzyme system in extracts of wild-type (Ino+) cells. J Bacteriol. 1976 Apr;126(1):232–242. doi: 10.1128/jb.126.1.232-242.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Culbertson M. R., Henry S. A. Inositol-requiring mutants of Saccharomyces cerevisiae. Genetics. 1975 May;80(1):23–40. doi: 10.1093/genetics/80.1.23. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Daum G. Lipids of mitochondria. Biochim Biophys Acta. 1985 Jun 12;822(1):1–42. doi: 10.1016/0304-4157(85)90002-4. [DOI] [PubMed] [Google Scholar]
  9. Greenberg M. L., Goldwasser P., Henry S. A. Characterization of a yeast regulatory mutant constitutive for synthesis of inositol-1-phosphate synthase. Mol Gen Genet. 1982;186(2):157–163. doi: 10.1007/BF00331845. [DOI] [PubMed] [Google Scholar]
  10. Greenberg M. L., Klig L. S., Letts V. A., Loewy B. S., Henry S. A. Yeast mutant defective in phosphatidylcholine synthesis. J Bacteriol. 1983 Feb;153(2):791–799. doi: 10.1128/jb.153.2.791-799.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Greenberg M. L., Reiner B., Henry S. A. Regulatory mutations of inositol biosynthesis in yeast: isolation of inositol-excreting mutants. Genetics. 1982 Jan;100(1):19–33. doi: 10.1093/genetics/100.1.19. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Henry S. A., Klig L. S., Loewy B. S. The genetic regulation and coordination of biosynthetic pathways in yeast: amino acid and phospholipid synthesis. Annu Rev Genet. 1984;18:207–231. doi: 10.1146/annurev.ge.18.120184.001231. [DOI] [PubMed] [Google Scholar]
  13. Hirsch J. P., Henry S. A. Expression of the Saccharomyces cerevisiae inositol-1-phosphate synthase (INO1) gene is regulated by factors that affect phospholipid synthesis. Mol Cell Biol. 1986 Oct;6(10):3320–3328. doi: 10.1128/mcb.6.10.3320. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Homann M. J., Henry S. A., Carman G. M. Regulation of CDP-diacylglycerol synthase activity in Saccharomyces cerevisiae. J Bacteriol. 1985 Sep;163(3):1265–1266. doi: 10.1128/jb.163.3.1265-1266.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Jones E. W. The synthesis and function of proteases in Saccharomyces: genetic approaches. Annu Rev Genet. 1984;18:233–270. doi: 10.1146/annurev.ge.18.120184.001313. [DOI] [PubMed] [Google Scholar]
  16. Klig L. S., Homann M. J., Carman G. M., Henry S. A. Coordinate regulation of phospholipid biosynthesis in Saccharomyces cerevisiae: pleiotropically constitutive opi1 mutant. J Bacteriol. 1985 Jun;162(3):1135–1141. doi: 10.1128/jb.162.3.1135-1141.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kuchler K., Daum G., Paltauf F. Subcellular and submitochondrial localization of phospholipid-synthesizing enzymes in Saccharomyces cerevisiae. J Bacteriol. 1986 Mar;165(3):901–910. doi: 10.1128/jb.165.3.901-910.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Loewy B. S., Henry S. A. The INO2 and INO4 loci of Saccharomyces cerevisiae are pleiotropic regulatory genes. Mol Cell Biol. 1984 Nov;4(11):2479–2485. doi: 10.1128/mcb.4.11.2479. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Waechter C. J., Lester R. L. Differential regulation of the N-methyl transferases responsible for phosphatidylcholine synthesis in Saccharomyces cerevisiae. Arch Biochem Biophys. 1973 Sep;158(1):401–410. doi: 10.1016/0003-9861(73)90637-1. [DOI] [PubMed] [Google Scholar]
  20. Yamashita S., Oshima A., Nikawa J., Hosaka K. Regulation of the phosphatidylethanolamine methylation pathway in Saccharomyces cerevisiae. Eur J Biochem. 1982 Nov 15;128(2-3):589–595. doi: 10.1111/j.1432-1033.1982.tb07005.x. [DOI] [PubMed] [Google Scholar]

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