, Volume 46, Issue 6, pp 569–579 | Cite as

Lipid transport pathways in mammalian cells

  • D. R. Voelker


A major deficit in our understanding of membrane biogenesis in eukaryotes is the definition of mechanisms by which the lipid constituents of cell membranes are transported from their sites of intracellular synthesis to the multiplicity of membranes that constitute a typical cell. A variety of approaches have been used to examine the transport of lipids to different organelles. In many cases the development of new methods has been necessary to study the problem. These methods include cytological examination of cells labeled with fluorescent lipid analogs, improved methods of subcellular fractionation, in situ enzymology that demonstrates lipid translocation by changes in lipid structure, and cell-free reconstitution with isolated organelles. Several general patterns of lipid transport have emerged but there does not appear to be a unifying mechanism by which lipids move among different organelles. Significant evidence now exists for vesicular and metabolic energy-dependent mechanisms as well as mechanisms that are clearly independent of cellular ATP content.

Key words

Lipids membranes transport organelles vesicles 


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  1. 1.
    Backer, J. M., and Dawidowicz, E. A., Reconstitution of a phospholipid flippase from rat liver microsomes. Nature327 (1987) 341–343.Google Scholar
  2. 2.
    Bevers, E. M., Comfurius, P., and Zwall, R. F. A., Changes in membrane phospholipid distribution during platelet activation. Biochim. biophys. Acta736 (1983) 57–66.Google Scholar
  3. 3.
    Bishop, W. R., and Bell, R. M., Assembly of phospholipids into cellular membranes: biosynthesis, transmembrane movement and intracellular translocation. A. Rev. Cell Biol.4 (1988) 579–610.Google Scholar
  4. 4.
    Chanderbhan, R., Noland, B. J., Scallen, T. J., and Vahouny, G. V., Sterol carrier protein2. J. biol. Chem.257 (1982) 8928–8934.Google Scholar
  5. 5.
    Colbeau, A., Machbaur, J., and Vignais, P. M., Enzymic characterization and lipid composition of rat liver subcellular membranes. Biochim. biophys. Acta249 (1970) 462–492.Google Scholar
  6. 6.
    Crivello, J. F., and Jefcoate, C. R., Intracellular movement of cholesterol in rat adrenal cells. J. biol. Chem.255 (1980) 8144–8151.Google Scholar
  7. 7.
    Daleke, D. L., and Huestis, W. H., Incorporation and translocation of aminophospholipids in human erythrocytes. Biochemistry24 (1985) 5406–5416.Google Scholar
  8. 8.
    Dawidowicz, E. A., Dynamics of membrane lipid metabolism and turnover. A. Rev. Biochem.56 (1987) 43–61.Google Scholar
  9. 9.
    DeGrella, R. F., and Simoni, R. D., Intracellular transport of cholesterol to the plasma membrane. J. biol. Chem.257 (1982) 14256–14262.Google Scholar
  10. 10.
    Dennis, E. A., and Kennedy, E. P., Intracellular sites of lipid synthesis and the biogenesis of mitochondria. J. Lipid Res.13 (1972) 263–267.Google Scholar
  11. 11.
    Devaux, P. F., Phospholipids flippases. FEBS Lett.234 (1988) 8–12.Google Scholar
  12. 12.
    Devaux, P. F., and Zachowski, A., Transmembrane movement of lipids. Experientia46 (1990) 644–656.Google Scholar
  13. 13.
    Esko, J. D., Nishijima, M., and Raetz, C. R. H., Animal cells dependent on exogenous phosphatidylcholine for membrane biogenesis. Proc. natl Acad. Sci. USA79 (1982) 1698–1702.Google Scholar
  14. 14.
    Esko, J. D., and Raetz, C. R. H., Synthesis of phospholipids in animal cells, in: The Enzymes, vol. 16, pp. 208–253. Ed. P. D. Boyer. Academic Press, New York 1983.Google Scholar
  15. 15.
    Helmy, S., Porter-Jordan, K., Dawidowicz, E. A., Pilch, P., Schwartz, A. L., and Fine, R. E., Separation of endocytic from exocytic coated vesicles using a novel cholinesterase mediated density shift technique. Cell44 (1986) 497–506.Google Scholar
  16. 16.
    Jelsema, C. L., and Morre, D. J., Distribution of phospholipid biosynthetic enzymes among cell components of rat liver. J. biol. Chem. 253 (1978) 7960–7971.Google Scholar
  17. 17.
    Kaplan, M. R., and Simoni, R. D., Intracellular transport of phosphatidylcholine to the plasma membrane. J. Cell Biol.101 (1985) 441–445.Google Scholar
  18. 18.
    Kaplan, M. R., and Simoni, R. D., Transport of cholesterol from the endoplasmic reticulum to the plasma membrane. J. Cell Biol.101 (1985) 446–453.Google Scholar
  19. 19.
    Kawashima, Y., and Bell, R. M., Assembly of the endoplasmic reticulum bilayer. Transporter for phosphatidylcholine and metabolites. J. biol. Chem.262 (1987) 16495–16502.Google Scholar
  20. 20.
    Keenan, T. W., and Morre, D. J., Phospholipid class and fatty acid composition of Golgi apparatus isolated from rat liver and comparison with other cell fractions. Biochemistry9 (1970) 19–24.Google Scholar
  21. 21.
    Kobayashi, T., and Pagano, R. E., Lipid transport during mitosis. J. biol. Chem.264 (1989) 5966–5973.Google Scholar
  22. 22.
    Koval, M., and Pagano, R. E., Lipid recycling between the plasma membrane and intracellular compartments: Transport and metabolism of fluorescent sphingomyelin analogues in cultured fibroblasts. J. Cell Biol.108 (1989) 2169–2181.Google Scholar
  23. 23.
    Lambeth, J. D., Xu, X. X., and Glover, M., Cholesterol sulfate inhibits adrenal mitochondrial cholesterol side chain cleavage at a site distinct from cytochrome P-450scc. J. biol. Chem.262 (1987) 9181–9188.Google Scholar
  24. 24.
    Lange, Y., and Matthies, H. J. G., Transfer of cholesterol from its site of synthesis to the plasma membrane. J. biol. Chem.259 (1984) 14624–14630.Google Scholar
  25. 25.
    Lange, Y., and Muraski, M. F., Topographic heterogeneity in cholesterol biosynthesis. J. biol. Chem.263 (1988) 9366–9373.Google Scholar
  26. 26.
    Lange, Y., Swaisgood, M. H., Ramos, B. V., and Steck, T. L., Plasma membranes contain half the phospholipid and 90% of the cholesterol and sphingomyelin in cultured human fibroblasts. J. biol. Chem.264 (1989) 3786–3793.Google Scholar
  27. 27.
    Lipsky, N. G., and Pagano, R. E., Sphingolipid metabolism in cultured fibroblasts: microscopic and biochemical studies employing a fluorescent ceramide analogue. Proc. natl Acad. Sci. USA80 (1983) 2608–2612.Google Scholar
  28. 28.
    Lipsky, N. G., and Pagano, R. E., Intracellular translocation of fluorescent sphingolipids in cultured fibroblasts: endogeneously synthesized sphingomyelin and glucocerebroside analogues pass through the Golgi apparatus en route to the plasma membrane. J. Cell Biol.100 (1985) 27–34.Google Scholar
  29. 29.
    Martin, O. C., and Pagano, R. E., Transbilayer movement of fluorescent analogs of phosphatidylserine and phosphatidylethanolamine at the plasma membrane of cultured cells. J. biol. Chem.262 (1987) 5890–5898.Google Scholar
  30. 30.
    Miller, M. A., and Kent, C., Characterization of the pathways for phosphatidylethanolamine biosynthesis in Chinese hamster ovary mutant and parental cell lines. J. biol. Chem.261 (1986) 9753–9761.Google Scholar
  31. 31.
    Nishijima, M., Kuge, O., and Akamatsu, Y., Phosphatidylserine biosynthesis in cultured Chinese hamster ovary cells. J. biol. Chem.261 (1986) 5784–5789.Google Scholar
  32. 32.
    Op den Kamp, J. A. F., Lipid asymmetry in membranes. A. Rev. Biochem.48 (1979) 47–71.Google Scholar
  33. 33.
    Orci, L., Montesano, R., Meda, P., Malaise-Lagal, F., Brown, D., Perrelet, A., and Vassali, P., Heterogenous distribution of fillipincholesterol complexes across the cysternae of the Golgi apparatus. Proc. natl Acad. Sci. USA78 (1981) 293–297.Google Scholar
  34. 34.
    Pagano, R. E., and Longmuir, K. J., Phosphorylation, transbilayer movement, and facilitated intracellular transport of diacylglycerol are involved in the uptake of a fluorescent analog of phosphatidic acid by cultured fibroblasts. J. biol. Chem.260 (1985) 1909–1916.Google Scholar
  35. 35.
    Pagano, R. E., Longmuir, K. J., and Martin, O. C., Intracellular translocation and metabolism of a fluorescent phosphatidic acid analogue in cultured fibroblasts. J. biol. Chem.258 (1983) 2034–2040.Google Scholar
  36. 36.
    Pagano, R. E., and Sleight, R. G., Defining lipid transport pathways in animal cells. Science229 (1985) 1051–1057.Google Scholar
  37. 37.
    Poznansky, M. J., and Czekanski, S., Cholesterol movement between human skin fibroblasts and phosphatidylcholine vesicles. Biochim. biophys. Acta685 (1982) 182–190.Google Scholar
  38. 38.
    Reinhart, M. P., Intracellular sterol trafficking. Experientia46 (1990) 599–611.Google Scholar
  39. 39.
    Reinhart, M. P., Billheimer, J. T., Faust, J. R., and Gaylor, J. L., Subcellular localization of the enzymes of cholesterol biosynthesis and metabolism in rat liver. J. biol. Chem.262 (1987) 9649–9655.Google Scholar
  40. 40.
    Robertson, D. L., and Poznansky, M. J., The effect of non-receptor-mediated uptake of cholesterol on intracellular cholesterol metabolism in human skin fibroblasts. Biochem. J.232 (1990) 553–557.Google Scholar
  41. 41.
    Sandra, A., and Pagano, R. E., Phospholipid asymmetry in LM cell plasma membrane derivatives: Polar head group and acyl chain distributions. Biochemistry17 (1978) 332–338.Google Scholar
  42. 42.
    Schroit, A. J., Madsen, J. W., and Tanaka, Y., In vivo recognition and clearance of red blood cells containing phosphatidylserine in their plasma membranes. J. biol. Chem.260 (1985) 5131–5138.Google Scholar
  43. 43.
    Siegneuret, M., and Devaux, P. F., ATP-dependent asymmetric distribution of spin-labeled phospholipids in the erythrocyte membrane: Relation to shape changes. Proc. natl Acad. Sci. USA81 (1984) 3751–3755.Google Scholar
  44. 44.
    Simons, K., and van Meer, G., Lipid sorting in epithelial cells. Biochemistry27 (1988) 6197–6202.Google Scholar
  45. 45.
    Sleight, R. G., Intracellular lipid transport in eukaryotes. A. Rev. Physiol.49 (1987) 193–208.Google Scholar
  46. 46.
    Sleight, R. G., and Abanto, M. N., Differences in intracellular transport of a fluorescent phosphatidylcholine analog in established cell lines. J. Cell Sci.93 (1989) 363–374.Google Scholar
  47. 47.
    Sleight, R. G., and Pagano, R. E., Rapid appearance of newly synthesized phosphatidylethanolamine at the plasma membrane. J. biol. Chem.258 (1983) 9050–9058.Google Scholar
  48. 48.
    Sleight, R. G., and Pagano, R. E., Transport of a fluorescent phosphatidylcholine analog from the plasma membrane to the Golgi apparatus. J. Cell Biol.99 (1984) 742–751.Google Scholar
  49. 49.
    Sleight, R. G., and Pagano, R. E., Transbilayer movement of a fluorescent phosphatidylethanolamine analogue across the plasma membranes of cultured mammalian cells. J. biol. Chem.260 (1985) 1146–1154.Google Scholar
  50. 50.
    Slotte, J. P., and Lundberg, B., Transfer of (3H)-cholesterol between lipid vesicles and rat arterial smooth muscle in vitro. Biochim. biophys. Acta750 (1983) 434–439.Google Scholar
  51. 51.
    Slotte, J. P., Lundberg, B., and Bjorkernd, S., Intracellular transport and esterification of exchangeable cholesterol in cultured human lung fibroblasts. Biochim. biophys. Acta793 (1984) 423–428.Google Scholar
  52. 52.
    Spiegel, S., Blumenthal, R., Fishman, P. H., and Handler, J. S., Gangliosides do not move from apical to basolateral plasma membrane in cultured epithelial cells. Biochim. biophys. Acta821 (1985) 310–318.Google Scholar
  53. 53.
    Tilley, L., Criber, S., Roelofsen, B., Op de Kamp, J. A. F., and van Deenen, L. L. M., ATP-dependent translocation of amino phospholipids across the human erythrocyte membrane. FEBS Lett.194 (1986) 21–27.Google Scholar
  54. 54.
    Vance, J. E., and Vance, D. E., Does rat liver Golgi have the capacity to synthesize phospholipids for lipoprotein secretion? J. biol. Chem.263 (1988) 5898–5909.Google Scholar
  55. 55.
    Vance, D. E., and Vance, J. E., Specific pools of phospholipids are used for lipoprotein secretion by cultured rat hepatocytes. J. biol. Chem.261 (1986) 4486–4491.Google Scholar
  56. 56.
    Van Golde, L. M. G., Raben, J., Batenburg, J. J., Fleischer, B., Zambrano, F., and Fleischer, S., Biosynthesis of lipids in Golgi complex and other subcellular fractions from rat liver. Biochim. biophys. Acta360 (1974) 179–192.Google Scholar
  57. 57.
    van Meer, G., Biosynthetic lipid traffic in animal eukaryotes. A. Rev. Cell Biol.5 (1989) 247–275.Google Scholar
  58. 58.
    van Meer, G., Stelzer, E. H. K., Wijnaendts-van-Resandt, R. W., and Simons, K., Sorting of sphingolipids in epithelial (Madin-Darby Canine Kidney) cells. J. Cell Biol.105 (1987) 1623–1635.Google Scholar
  59. 59.
    Verkleij, A. J., Zwaal, R. F. A., Roelofsen, B., Comfurius, P., Kastelijn, D., and van Deenen, L. L. M., The asymmetric distribution of phospholipids in the human red cell membrane. A combined study using phospholipases and freeze-etching electron microscopy. Biochim. biophys. Acta323 (1973) 178–193.Google Scholar
  60. 60.
    Voelker, D. R., Lipid assembly into cell membranes, in: Biochemistry of Lipids and Membranes, pp. 475–502. Eds D. E. Vance and J. E. Vance. Benjamin Cummings, California 1985.Google Scholar
  61. 61.
    Voelker, D. R., Phosphatidylserine functions as the major precursor of phosphatidylethanolamine in cultured BHK 21 cells. Proc. natl Acad. Sci. USA81 (1984) 2669–2673.Google Scholar
  62. 62.
    Voelker, D. R., Disruption of phosphatidylserine translocation to the mitochondria in baby hamster kidney cells. J. biol. Chem.260 (1985) 14671–14676.Google Scholar
  63. 63.
    Voelker, D. R., Reconstitution of phosphatidylserine import into rat liver mitochondria. J. biol. Chem.264 (1989) 8019–8025.Google Scholar
  64. 64.
    Voelker, D. R., Phosphatidylserine translocation to the mitochondrion is an ATP dependent process in permeabilized animal cells. Proc. natl Acad. Sci. USA86 (1989) 9921–9925.Google Scholar
  65. 65.
    Voelker, D. R., and Frazier, J. L., Isolation and characterization of a Chinese hamster ovary cell line requiring ethanolamine or phosphatidylserine for growth and exhibiting defective phosphatidylserine synthase activity. J. biol. Chem.261 (1986) 1002–1008.Google Scholar
  66. 66.
    Wirtz, K. W. A., and Gadella, T. W. J., Properties and modes of action of specific and non-specific phospholipid transfer proteins. Experientia46 (1990) 592–599.Google Scholar
  67. 67.
    Wirtz, K. W. A., and Zilversmit, D. B., Exchange of phospholipids between liver mitochondria and microsomes in vitro. J. biol. Chem.243 (1968) 3596–3602.Google Scholar
  68. 68.
    Yaffe, M. P., and Kennedy, E. P., Intracellular phospholipid movement and the role of phospholipid transfer proteins in animal cells. Biochemistry22 (1983) 1497–1507.Google Scholar
  69. 69.
    Zachowski, A., Favre, E., Cribier, S., Hervé, P., and Devaux, P. F., Outside-inside translocation of aminophospholipids in the human erythrocyte membrane is mediated by a specific enzyme. Biochemistry25 (1986) 2585–2590.Google Scholar
  70. 70.
    Zachowski, A., Fellman, P., and Devaux, P. F., Absence of transbilayer diffusion of spin-labeled sphingomyelin on human erythrocytes. Comparison with diffusion of several spin-labeled glycerophospholipids. Biochim. biophys. Acta815 (1985) 510–514.Google Scholar

Copyright information

© Birkhäuser Verlag 1990

Authors and Affiliations

  • D. R. Voelker
    • 1
  1. 1.Department of MedicineThe National Jewish Center of Immunology and Respiratory MedicineDenverUSA

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