Role of Phospholipids in Cell Function

  • William Dowhan
Conference paper
Part of the NATO ASI Series book series (volume 82)


A primary and essential role for phospholipids is defining the permeability barrier of the cell membrane and all internal organelles. However, due to the molecular diversity of phospholipids, individual phospholipid species must play a more dynamic role in cell function than simply defining the physical properties of the membrane. In addition to forming the membrane permeability barrier, phospholipids are intermediates in the synthesis of or direct precursors to other cellular components as well as regulatory molecules which affect cell physiology. Because of this pleiotropic requirement for phospholipids in maintaining normal cell function, it has often been difficult to assign a specific role to a particular phospholipid or group of phospholipids through in vivo studies. There are no direct assays for phospholipids function, as there are for enzymes, so the functions of individual phospholipids have come to light in many cases incidental to the study of a particular cellular process in vitro rather than by direct study of a particular phospholipid. In most cell types it is difficult to effect systematic and extensive alteration of the normal phospholipid composition which has made it difficult to verify in vivo the physiological significance of functions deduced from in vitro biochemical approaches alone. Utilization of classical genetic approaches has established the essential role of specific phospholipids for cell viability but has not provided a precise understanding at the molecular level for their requirement (Raetz and Dowhan, 1990). Application of more direct approaches of modern molecular genetics has made possible the design of mutants in which phospholipid metabolism and therefore phospholipid composition can be more precisely controlled (Dowhan, 1992). With such mutants it has been possible to establish new in vivo roles for phospholipids which has lead to biochemical studies to define the molecular basis for these functions.


NADH Dehydrogenase Phospholipid Composition Phospholipid Metabolism Acidic Phospholipid DnaA Protein 
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  1. Asai Y, Katayose Y, Hikita C, Ohta A, Shibuya I (1989) Suppression of the lethal effect of acidic-phospholipid deficiency by defective formation of the major outer membrane lipoprotein in Escherichia coli. J Bacteriol 171: 6867–6869PubMedGoogle Scholar
  2. Bogdanov M, Dowhan W (1993) Phosphatidylethanolamine (PE) is required fro in vivo function of the lactose permease of Escherichia coli. FASEB J 7: A518Google Scholar
  3. Chen C-C Wilson TH (1984) The phospholipid requirement for activity of the lactose carrier of E. coli. J Biol Chem 259: 10150–10158PubMedGoogle Scholar
  4. Crooke E, Castuma CE, Kornberg A. (1992) The chromosome origin of E. colistabilizes DnaA protein during rejuvenation by phospholipids. J Biol Chem 267: 16779–16782PubMedGoogle Scholar
  5. DeChavigny A, Heacock PN, Dowhan W (1991) Sequence and Inactivation of the pssgene of Escherichia coli. J Biol Chem 266: 5323–5332PubMedGoogle Scholar
  6. Dowhan, W (1992) Strategies of generating and utilizing phospholipid synthesis mutants in Escherichia coli. Method in Enzymol (Dennis EA, Vance DE, eds.) 209:7–20Google Scholar
  7. Dowhan W, Heacock PN (1987) Construction of a lethal mutation in the synthesis of the major acidic phospholipids of Escherichia coli. J Biol Chem 262: 13044–13049PubMedGoogle Scholar
  8. Dutt A, Dowhan W, (1977) Intracellular distribution of enzymes of phospholipid metabolism in several Gram-negative bacteria. J Bacteriol 132: 159–165PubMedGoogle Scholar
  9. Funk CR, Zimniak L, Dowhan W (1992) The pgpAand pgpBgenes of Escherichia coliare not essential: Evidence for a third phosphatidylglycerophosphate phosphatase. J Bacteriol 174: 205–213PubMedGoogle Scholar
  10. Ganong BR, Leonard JM, Raetz CRH (1980) Phosphatidic acid accumulation in the membranes of Escherichia colimutants defective in CDP-diglyceride synthetase. J Biol Chem 255: 1623–1629PubMedGoogle Scholar
  11. Gangola P, Rosen BP (1987) Maintenance of intracellular calcium in Escherichia coli. J Biol Chem 262: 12570–12574PubMedGoogle Scholar
  12. Hawrot E, Kennedy EP (1978) Phospholipid composition and membrane function in phosphatidylserine decarboxylase mutants of Escherichia coli. J Biol Chem 253: 8213–8220PubMedGoogle Scholar
  13. Heacock PN, Dowhan W (1989) Alteration of the phospholipids composition of Escherichia colithrough genetic manipulation. J Biol Chem 264: 14972–14977PubMedGoogle Scholar
  14. Hendrick JP, Wickner W (1991) SecA protein needs both acidic phospholipids and SecY/E protein for functional high-affinity binding to the Escherichia coliplasma membrane. J Biol Chem 266: 24596–24600PubMedGoogle Scholar
  15. Horiuchi T, Maki H, Sekiguchi M. (1984) RNase H-defective mutants of E. coli: A possible discriminatory role of RNase H in initiation of DNA replication. Mol Gen Genet 195: 17–22PubMedCrossRefGoogle Scholar
  16. Icho T, Raetz CRH (1983) Multiple genes for membrane-bound phosphatase in Escherichia coliand their action on phospholipid precursors. J Bacteriol 153: 722–730PubMedGoogle Scholar
  17. Jackowski S, Cronan, Jr. JE, Rock CO (1991) Lipid metabolism in procaryotes. InBiochemistry of lipids, lipoproteins and membranes. ( Vance DE, Vance J, eds) Elsevier Sci. Publ. B. V., Amsterdam, 43–85Google Scholar
  18. Kogoma T, von Meyenburg K (1983) The origin of replication, oriC, and the dnaAprotein are dispensable in stable DNA replication (sdrA)mutants of E. coliK-12. EMBO J 2: 463–468PubMedGoogle Scholar
  19. Kuge O, Nishijima M, Akamatsu Y (1991) A cloned gene encoding phosphatidylserine decarboxylase complements the phosphatidylserine biosynthetic defect of a Chinese hamster ovary mutant. J Biol Chem 266: 6370–6376PubMedGoogle Scholar
  20. Kusters R, Dowhan W, de Kruijff B (1991) Negatively charged phospholipids restore prePhoE translocation across phosphatidylglycerol-depleted Escherichia coliinner membranes. J Biol Chem 266: 8659–8662PubMedGoogle Scholar
  21. Lill R, Dowhan W, Wickner W (1990) The ATPase activity of SecA is regulated by acidic phospholipids, SecY, and the leader and mature domains of precursor proteins. Cell 60: 271–280PubMedCrossRefGoogle Scholar
  22. Louie C, Dowhan, W (1980) Investigations on the association of phosphatidylyserine synthase with the ribosomal component of Escherichia coli. J Biol Chem 255: 1124–1127PubMedGoogle Scholar
  23. Mileykovskaya EI, Dowhan W (1993) Alterations in the electron transfer chain in strains of Escherichia coli lacking phosphatidylethanolamine. J Biol Chem, in the pressGoogle Scholar
  24. Miyazaki C, Kuroda M, Ohta A, Shibuya I (1985) Genetic manipulation of membrane phospholipid composition in Escherichia coli: pgsAmutants defective in phosphatidylglycerol synthesis. Proc Natl Acad Sci USA 82: 7530–7534PubMedCrossRefGoogle Scholar
  25. Nishijima S, Asami Y, Uetake N, Yamogoe S, Ohta A, Shibuya I (1988) Disruption of the Escherichia coli clsgene responsible for cardiolipin synthesis. J Bacteriol 170: 775–780PubMedGoogle Scholar
  26. Nishijima M, Raetz CRH (1979) Membrane lipid biogenesis in Escherichia coli: Identification of genetic loci for phosphatidylglycerophosphate synthetase and construction of mutants lacking phosphatidylglycerol. J Biol Chem 254: 7837–7844PubMedGoogle Scholar
  27. Ohta A, Shibuya I (1977) Membrane phospholipid synthesis and phenotypic correlation of an Esch?richia coli pssmutant. J Bacteriol 132: 434–443PubMedGoogle Scholar
  28. Raetz CRH (1986) Molecular genetics of membrane phospholipid synthesis. Annu Rev Genet 20: 253–295PubMedCrossRefGoogle Scholar
  29. Raetz CRH (1990) Biochemistry of endotoxins. Annu Rev Biochem 59: 129–70.PubMedCrossRefGoogle Scholar
  30. Raetz CRH, Dowhan W (1990) Biosynthesis and function of phospholipids in Escherichia coli. J Biol Chem 265: 1235–1238PubMedGoogle Scholar
  31. Raetz CRH, Kantor GD, Nishijima M, Newman KF (1979) Cardiolipin accumulation in the inner and outer membranes of Escherichia colimutants defective in phosphatidylserine synthetase. J Bacteriol 139: 544–551PubMedGoogle Scholar
  32. Reitveld, AG, Killian A, Dowhan W, de Kruijff B (1993) Polymorphic regulation of membrane phospholipid composition in Escherichia coli. J Biol Chem, in the pressGoogle Scholar
  33. Shibuya I (1992) Metabolic regulations and biological functions of phospholipids in Escherichia coli. Prog Lipid Res 31: 245–299PubMedCrossRefGoogle Scholar
  34. Shibuya I, Miyazaki C, Ohta A (1985) Alteration of phospholipid composition by combined defects in phosphatidylserine and cardiolipin synthases and physiological consequences in Escherichia coli. J Bacteriol 161: 1086–1092PubMedGoogle Scholar
  35. Sekimizu K, Kornberg A (1988) Cardiolipin activation of dnaA protein, the initiation protein of replication in E. coli. J Biol Chem 263: 7131–7153PubMedGoogle Scholar
  36. Sparrow CP, Raetz CRH (1985) Purification and properties of the membrane-bound CDP-diglyceride synthetase of Escherichia coli. J Biol Chem 260: 12084–12091PubMedGoogle Scholar
  37. Vanden Boom T, Cronan, Jr. JE (1989) Genetics and regulation of bacterial lipid metabolism. Annu Rev Microbiol 43: 317–343CrossRefGoogle Scholar
  38. Van der Goot FG, Didat N, Pattus F, Dowhan W, Letellier L (1993) Role of acidic lipids in the translocation and channel activity of colicins A and N in Escherichia coli. Eur J Biochem 213: 217–221PubMedCrossRefGoogle Scholar
  39. Vasilenko I, de Kruijff B, Verkleij AJ (1982) Polymorphic phase behavior of cardiolipin from bovine heart and from Bacillus subtilisas detected by 31P-NMR and freeze-fracture. Biochim Biophys Acta 684: 282–286PubMedCrossRefGoogle Scholar
  40. Wu HC, Tokunaga M, Tokunaga H, Hayashi S, Giam C-Z (1983) Posttranslational modification and processing of membrane lipoproteins in bacteria. J Cell Biochem 22: 161–171PubMedCrossRefGoogle Scholar
  41. Yung BY-M, Kornberg A (1988) Membrane attachment activates DnaA protein, the initiation protein of chromosome replication in Escherichia coli. Proc Natl Acad Sci USA 85: 7202–7205PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1994

Authors and Affiliations

  • William Dowhan
    • 1
  1. 1.Department of Biochemistry and Molecular BiologyUniversity of Texas Medical SchoolHoustonUSA

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