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The biophysics and cell biology of lipid droplets

Nature Reviews Molecular Cell Biology volume 14, pages 775–786 (2013)Cite this article

Subjects

Key Points

  • Cellular lipid droplets store lipids as reservoirs for metabolic energy and membrane precursors.

  • Lipid droplets form the dispersed phase of a cellular emulsion in the aqueous cytosol.

  • Principles of emulsion science are applicable to many lipid droplet-related processes.

  • Emulsions properties, such as lipid droplet size, are governed by surface properties of the phase interface.

  • Different lipids and proteins can modulate lipid droplet surface properties and hence lipid droplet biology.

Abstract

Lipid droplets are intracellular organelles that are found in most cells, where they have fundamental roles in metabolism. They function prominently in storing oil-based reserves of metabolic energy and components of membrane lipids. Lipid droplets are the dispersed phase of an oil-in-water emulsion in the aqueous cytosol of cells, and the importance of basic biophysical principles of emulsions for lipid droplet biology is now being appreciated. Because of their unique architecture, with an interface between the dispersed oil phase and the aqueous cytosol, specific mechanisms underlie their formation, growth and shrinkage. Such mechanisms enable cells to use emulsified oil when the demands for metabolic energy or membrane synthesis change. The regulation of the composition of the phospholipid surfactants at the surface of lipid droplets is crucial for lipid droplet homeostasis and protein targeting to their surfaces.

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Figure 1: Basic principles of emulsion physics relevant to lipid droplets.
Figure 2: Processes that govern changes in lipid droplet size.
Figure 3: Binding mode of proteins.
Figure 4: Models for mechanisms of lipid droplet formation.
Figure 5: Consumption and utilization of lipid droplets.

References

  1. Walther, T. C. & Farese, R. V. Jr. Lipid droplets and cellular lipid metabolism. Annu. Rev. Biochem. 81, 687–714 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Brasaemle, D. L. & Wolins, N. E. Packaging of fat: an evolving model of lipid droplet assembly and expansion. J. Biol. Chem. 287, 2273–2279 (2012).

    Article  CAS  PubMed  Google Scholar 

  3. Fujimoto, T. & Parton, R. G. Not just fat: the structure and function of the lipid droplet. Cold Spring Harb. Perspect. Biol. 3, a004838 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Thiele, C. & Spandl, J. Cell biology of lipid droplets. Curr. Opin. Cell Biol. 20, 378–385 (2008).

    Article  CAS  PubMed  Google Scholar 

  5. Krahmer, N., Farese, R. V. Jr & Walther, T. C. Balancing the fat: lipid droplets and human disease. EMBO Mol. Med. 5, 905–915 (2013).

    Article  CAS  PubMed Central  Google Scholar 

  6. Bartz, R. et al. Lipidomics reveals that adiposomes store ether lipids and mediate phospholipid traffic. J. Lipid Res. 48, 837–847 (2007).

    Article  CAS  PubMed  Google Scholar 

  7. Zanghellini, J., Wodlei, F. & von Grunberg, H. H. Phospholipid demixing and the birth of a lipid droplet. J. Theor. Biol. 264, 952–961 (2010).

    Article  CAS  PubMed  Google Scholar 

  8. Khandelia, H., Duelund, L., Pakkanen, K. I. & Ipsen, J. H. Triglyceride blisters in lipid bilayers: implications for lipid droplet biogenesis and the mobile lipid signal in cancer cell membranes. PLoS ONE 5, e12811 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Kabalnov, A. & Wennerström, H. Macroemulsion stability: the oriented wedge theory revisited. Langmuir 12, 276–292 (1996).

    Article  CAS  Google Scholar 

  10. Sjoblom, J. Encyclopedic handbook of emulsion technology (CRC Press, 2010).

    Google Scholar 

  11. Leal-Calderon, F., Schmitt, V. & Bibette, J. Emulsion science: basic principles (Springer, 2007).

    Google Scholar 

  12. Tauchi-Sato, K., Ozeki, S., Houjou, T., Taguchi, R. & Fujimoto, T. The surface of lipid droplets is a phospholipid monolayer with a unique fatty acid composition. J. Biol. Chem. 277, 44507–44512 (2002).

    Article  CAS  PubMed  Google Scholar 

  13. Roux, A. et al. Role of curvature and phase transition in lipid sorting and fission of membrane tubules. EMBO J. 24, 1537–1545 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Fryd, M. M. & Mason, T. G. Advanced nanoemulsions. Annu. Rev. Phys. Chem. 63, 493–518 (2012).

    Article  CAS  PubMed  Google Scholar 

  15. van Buuren, A. R., Tieleman, D. P., de Vlieg, J. & Berendsen, H. J. C. Cosurfactants lower surface tension of the diglyceride/water interface: a molecular dynamics study. Langmuir 12, 2570–2579 (1996).

    Article  CAS  Google Scholar 

  16. Fei, W. et al. A role for phosphatidic acid in the formation of 'supersized' lipid droplets. PLoS Genet. 7, e1002201 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Krahmer, N. et al. Phosphatidylcholine synthesis for lipid droplet expansion is mediated by localized activation of CTP:phosphocholine cytidylyltransferase. Cell Metab. 14, 504–515 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Langevin, D. Rheology of adsorbed surfactant monolayers at fluid surfaces. Annu. Rev. Fluid Mech. http://dx.doi.org/10.1146/annurev-fluid-010313-141403 (2013).

  19. Georgieva, D., Schmitt, V., Leal-Calderon, F. & Langevin, D. On the possible role of surface elasticity in emulsion stability. Langmuir 25, 5565–5573 (2009).

    Article  CAS  PubMed  Google Scholar 

  20. Kabalnov, A., Tarara, T., Arlauskas, R. & Weers, J. Phospholipids as emulsion stabilizers. J. Colloid Interface Sci. 184, 227–235 (1996).

    CAS  PubMed  Google Scholar 

  21. Thiam, A. R. et al. COPI buds 60-nm lipid droplets from reconstituted water–phospholipid–triacylglyceride interfaces, suggesting a tension clamp function. Proc. Natl Acad. Sci. USA 110, 13244–13249 (2013).

    Article  PubMed  Google Scholar 

  22. Chen, Z. & Rand, R. P. The influence of cholesterol on phospholipid membrane curvature and bending elasticity. Biophys. J. 73, 267–276 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Chernomordik, L. V. & Kozlov, M. M. Protein–lipid interplay in fusion and fission of biological membranes. Annu. Rev. Biochem. 72, 175–207 (2003).

    Article  CAS  PubMed  Google Scholar 

  24. Koestler, D. C. et al. Blood-based profiles of DNA methylation predict the underlying distribution of cell types: a validation analysis. Epigenetics http://dx.doi.org/10.4161/epi.25430 (2013).

  25. Bremond, N., Thiam, A. R. & Bibette, J. Decompressing emulsion droplets favors coalescence. Phys. Rev. Lett. 100, 024501 (2008).

    Article  CAS  PubMed  Google Scholar 

  26. Thiam, A. R., Bremond, N. & Bibette, J. Breaking of an emulsion under an ac electric field. Phys. Rev. Lett. 102, 188304 (2009).

    Article  CAS  PubMed  Google Scholar 

  27. Bremond, N. & Bibette, J. Exploring emulsion science with microfluidics. Soft Matter 8, 10549–10559 (2012).

    Article  CAS  Google Scholar 

  28. Aarts, D. G., Schmidt, M. & Lekkerkerker, H. N. Direct visual observation of thermal capillary waves. Science 304, 847–850 (2004).

    Article  CAS  PubMed  Google Scholar 

  29. Leikin, S., Kozlov, M. M., Fuller, N. L. & Rand, R. P. Measured effects of diacylglycerol on structural and elastic properties of phospholipid membranes. Biophys. J. 71, 2623–2632 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. De Gennes, P.-G., Brochard-Wyart, F. & Quéré, D. Capillarity and wetting phenomena: drops, bubbles, pearls, waves (Springer, 2004).

    Book  Google Scholar 

  31. Karatekin, E. et al. Cascades of transient pores in giant vesicles: line tension and transport. Biophys. J. 84, 1734–1749 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Biswas, S., Yin, S. R., Blank, P. S. & Zimmerberg, J. Cholesterol promotes hemifusion and pore widening in membrane fusion induced by influenza hemagglutinin. J. Gen. Physiol. 131, 503–513 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Shemesh, T., Luini, A., Malhotra, V., Burger, K. N. & Kozlov, M. M. Prefission constriction of Golgi tubular carriers driven by local lipid metabolism: a theoretical model. Biophys. J. 85, 3813–3827 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Fernandez-Ulibarri, I. et al. Diacylglycerol is required for the formation of COPI vesicles in the Golgi-to-ER transport pathway. Mol. Biol. Cell 18, 3250–3263 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Popoff, V., Adolf, F., Brugger, B. & Wieland, F. COPI budding within the Golgi stack. Cold Spring Harb. Perspect. Biol. 3, a005231 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Kabalnov, A. & Weers, J. Kinetics of mass transfer in micellar systems: surfactant adsorption, solubilization kinetics, and ripening. Langmuir 12, 3442–3448 (1996).

    Article  CAS  Google Scholar 

  37. Kabalnov, A. S. Can micelles mediate a mass transfer between oil droplets? Langmuir 10, 680–684 (1994).

    Article  CAS  Google Scholar 

  38. Ariyaprakai, S. & Dungan, S. R. Influence of surfactant structure on the contribution of micelles to Ostwald ripening in oil-in-water emulsions. J. Colloid Interface Sci. 343, 102–108 (2010).

    Article  CAS  PubMed  Google Scholar 

  39. Baret, J. C. Surfactants in droplet-based microfluidics. Lab Chip 12, 422–433 (2012).

    Article  CAS  PubMed  Google Scholar 

  40. Hanczyc, M. M., Fujikawa, S. M. & Szostak, J. W. Experimental models of primitive cellular compartments: encapsulation, growth, and division. Science 302, 618–622 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Robenek, H., Robenek, M. J. & Troyer, D. PAT family proteins pervade lipid droplet cores. J. Lipid Res. 46, 1331–1338 (2005).

    Article  CAS  PubMed  Google Scholar 

  42. Paar, M. et al. Remodeling of lipid droplets during lipolysis and growth in adipocytes. J. Biol. Chem. 287, 11164–11173 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Ariotti, N. et al. Postlipolytic insulin-dependent remodeling of micro lipid droplets in adipocytes. Mol. Biol. Cell 23, 1826–1837 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Gong, J. et al. Fsp27 promotes lipid droplet growth by lipid exchange and transfer at lipid droplet contact sites. J. Cell Biol. 195, 953–963 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Jambunathan, S., Yin, J., Khan, W., Tamori, Y. & Puri, V. FSP27 promotes lipid droplet clustering and then fusion to regulate triglyceride accumulation. PLoS ONE 6, e28614 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Sun, Z. et al. Perilipin1 promotes unilocular lipid droplet formation through the activation of Fsp27 in adipocytes. Nature Commun. 4, 1594 (2013).

    Article  CAS  Google Scholar 

  47. Thiam, A. R., Bremond, N. & Bibette, J. From stability to permeability of adhesive emulsion bilayers. Langmuir 28, 6291–6298 (2012).

    Article  CAS  PubMed  Google Scholar 

  48. Grahn, T. H. et al. FSP27 and PLIN1 interaction promotes the formation of large lipid droplets in human adipocytes. Biochem. Biophys. Res. Commun. 432, 296–301 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Kabalnov, A. S. & Shchukin, E. D. Ostwald ripening theory: applications to fluorocarbon emulsion stability. Adv. Colloid Interface Sci. 38, 69–97 (1992).

    Article  CAS  Google Scholar 

  50. Greenberg, A. S. et al. Perilipin, a major hormonally regulated adipocyte-specific phosphoprotein associated with the periphery of lipid storage droplets. J. Biol. Chem. 266, 11341–11346 (1991).

    CAS  PubMed  Google Scholar 

  51. Londos, C. et al. Perilipin: unique proteins associated with intracellular neutral lipid droplets in adipocytes and steroidogenic cells. Biochem. Soc. Trans. 23, 611–615 (1995).

    Article  CAS  PubMed  Google Scholar 

  52. Cermelli, S., Guo, Y., Gross, S. P. & Welte, M. A. The lipid-droplet proteome reveals that droplets are a protein-storage depot. Curr. Biol. 16, 1783–1795 (2006).

    Article  CAS  PubMed  Google Scholar 

  53. Li, Z. et al. Lipid droplets control the maternal histone supply of Drosophila embryos. Curr. Biol. 22, 2104–2113 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Krahmer, N. et al. Protein correlation profiles identify lipid droplet proteins with high confidence. Mol. Cell Proteom. 12, 1115–1126 (2013).

    Article  CAS  Google Scholar 

  55. Brasaemle, D. L. et al. Perilipin A increases triacylglycerol storage by decreasing the rate of triacylglycerol hydrolysis. J. Biol. Chem. 275, 38486–38493 (2000).

    Article  CAS  PubMed  Google Scholar 

  56. Hinson, E. R. & Cresswell, P. The antiviral protein, viperin, localizes to lipid droplets via its N-terminal amphipathic α-helix. Proc. Natl Acad. Sci. USA 106, 20452–20457 (2009).

    Article  PubMed  Google Scholar 

  57. Taneva, S., Dennis, M. K., Ding, Z., Smith, J. L. & Cornell, R. B. Contribution of each membrane binding domain of the CTP:phosphocholine cytidylyltransferase-α dimer to its activation, membrane binding, and membrane cross-bridging. J. Biol. Chem. 283, 28137–28148 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Ding, Z. et al. A 22-mer segment in the structurally pliable regulatory domain of metazoan CTP:phosphocholine cytidylyltransferase facilitates both silencing and activating functions. J. Biol. Chem. 287, 38980–38991 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Mitsche, M. A. & Small, D. M. C-terminus of apolipoprotein A-I removes phospholipids from a triolein/phospholipids/water interface, but the N-terminus does not: a possible mechanism for nascent HDL assembly. Biophys. J. 101, 353–361 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Meyers, N. L., Wang, L. & Small, D. M. Apolipoprotein C-I binds more strongly to phospholipid/triolein/water than triolein/water interfaces: a possible model for inhibiting cholesterol ester transfer protein activity and triacylglycerol-rich lipoprotein uptake. Biochemistry 51, 1238–1248 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Abell, B. M. et al. Role of the proline knot motif in oleosin endoplasmic reticulum topology and oil body targeting. Plant Cell 9, 1481–1493 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Napier, J. A., Stobart, A. K. & Shewry, P. R. The structure and biogenesis of plant oil bodies: the role of the ER membrane and the oleosin class of proteins. Plant Mol. Biol. 31, 945–956 (1996).

    Article  CAS  PubMed  Google Scholar 

  63. Pol, A. et al. Cholesterol and fatty acids regulate dynamic caveolin trafficking through the Golgi complex and between the cell surface and lipid bodies. Mol. Biol. Cell 16, 2091–2105 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Le Lay, S. et al. Cholesterol-induced caveolin targeting to lipid droplets in adipocytes: a role for caveolar endocytosis. Traffic 7, 549–561 (2006).

    Article  CAS  PubMed  Google Scholar 

  65. Wilfling, F. et al. Triacylglycerol synthesis enzymes mediate lipid droplet growth by relocalizing from the ER to lipid droplets. Dev. Cell 24, 384–399 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Jacquier, N. et al. Lipid droplets are functionally connected to the endoplasmic reticulum in Saccharomyces cerevisiae. J. Cell Sci. 124, 2424–2437 (2011).

    Article  CAS  PubMed  Google Scholar 

  67. Waltermann, M. et al. Mechanism of lipid-body formation in prokaryotes: how bacteria fatten up. Mol. Microbiol. 55, 750–763 (2005).

    Article  CAS  PubMed  Google Scholar 

  68. Shum, H. C., Lee, D., Yoon, I., Kodger, T. & Weitz, D. A. Double emulsion templated monodisperse phospholipid vesicles. Langmuir 24, 7651–7653 (2008).

    Article  CAS  PubMed  Google Scholar 

  69. Hayward, R. C., Utada, A. S., Dan, N. & Weitz, D. A. Dewetting instability during the formation of polymersomes from block-copolymer-stabilized double emulsions. Langmuir 22, 4457–4461 (2006).

    Article  CAS  PubMed  Google Scholar 

  70. Li, Y., Kusumaatmaja, H., Lipowsky, R. & Dimova, R. Wetting-induced budding of vesicles in contact with several aqueous phases. J. Phys. Chem. B 116, 1819–1823 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Liu, Y., Lipowsky, R. & Dimova, R. Concentration dependence of the interfacial tension for aqueous two-phase polymer solutions of dextran and polyethylene glycol. Langmuir 28, 3831–3839 (2012).

    Article  CAS  PubMed  Google Scholar 

  72. Thiam, A. R., Bremond, N. & Bibette, J. Adhesive emulsion bilayers under an electric field: from unzipping to fusion. Phys. Rev. Lett. 107, 068301 (2011).

    Article  CAS  PubMed  Google Scholar 

  73. Kusumaatmaja, H. & Lipowsky, R. Droplet-induced budding transitions of membranes. Soft Matter 7, 6914–6919 (2011).

    Article  CAS  Google Scholar 

  74. Rosen, M. J. Surfactants and Interfacial Phenomena. 3rd edn Ch. 8 303–331 (Wiley, 2004).

    Book  Google Scholar 

  75. Safinya, C. R., Sirota, E. B., Roux, D. & Smith, G. S. Universality in interacting membranes: the effect of cosurfactants on the interfacial rigidity. Phys. Rev. Lett. 62, 1134–1137 (1989).

    Article  CAS  PubMed  Google Scholar 

  76. Kozlov, M. M. & Helfrich, W. Effects of a cosurfactant on the stretching and bending elasticities of a surfactant monolayer. Langmuir 8, 2792–2797 (1992).

    Article  CAS  Google Scholar 

  77. Gursoy, R. N. & Benita, S. Self-emulsifying drug delivery systems (SEDDS) for improved oral delivery of lipophilic drugs. Biomed. Pharmacother. 58, 173–182 (2004).

    Article  CAS  PubMed  Google Scholar 

  78. Pouton, C. W. Lipid formulations for oral administration of drugs: non-emulsifying, self-emulsifying and 'self-microemulsifying' drug delivery systems. Eur. J. Pharm. Sci. 11, S93–S98 (2000).

    Article  CAS  PubMed  Google Scholar 

  79. Sadurni, N., Solans, C., Azemar, N. & Garcia-Celma, M. J. Studies on the formation of O/W nano-emulsions, by low-energy emulsification methods, suitable for pharmaceutical applications. Eur. J. Pharm. Sci. 26, 438–445 (2005).

    Article  CAS  PubMed  Google Scholar 

  80. De Gennes, P. G. & Taupin, C. Microemulsions and the flexibility of oil/water interfaces. J. Phys. Chem. 86, 2294–2304 (1982).

    Article  CAS  Google Scholar 

  81. Langevin, D. Microemulsions. Accounts Chem. Res. 21, 255–260 (1988).

    Article  CAS  Google Scholar 

  82. Yamada, A. et al. Spontaneous transfer of phospholipid-coated oil-in-oil and water-in-oil micro-droplets through an oil/water interface. Langmuir 22, 9824–9828 (2006).

    Article  CAS  PubMed  Google Scholar 

  83. Stachowiak, J. C. et al. Membrane bending by protein–protein crowding. Nature Cell Biol. 14, 944–949 (2012).

    Article  CAS  PubMed  Google Scholar 

  84. Zimmerberg, J. & Kozlov, M. M. How proteins produce cellular membrane curvature. Nature Rev. Mol. Cell Biol. 7, 9–19 (2005).

    Article  CAS  Google Scholar 

  85. Wolins, N. E., Brasaemle, D. L. & Bickel, P. E. A proposed model of fat packaging by exchangeable lipid droplet proteins. FEBS Lett. 580, 5484–5491 (2006).

    Article  CAS  PubMed  Google Scholar 

  86. Cartwright, B. R. & Goodman, J. M. Seipin: from human disease to molecular mechanism. J. Lipid Res. 53, 1042–1055 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Fei, W., Du, X. & Yang, H. Seipin, adipogenesis and lipid droplets. Trends Endocrinol. Metab. 22, 204–210 (2011).

    Article  CAS  PubMed  Google Scholar 

  88. Hsieh, K. et al. Perilipin family members preferentially sequester to either triacylglycerol-specific or cholesteryl-ester-specific intracellular lipid storage droplets. J. Cell Sci. 125, 4067–4076 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Poppelreuther, M. et al. The N-terminal region of acyl-CoA synthetase 3 is essential for both the localization on lipid droplets and the function in fatty acid uptake. J. Lipid Res. 53, 888–900 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Brasaemle, D. L., Dolios, G., Shapiro, L. & Wang, R. Proteomic analysis of proteins associated with lipid droplets of basal and lipolytically stimulated 3T3-L1 adipocytes. J. Biol. Chem. 279, 46835–46842 (2004).

    Article  CAS  PubMed  Google Scholar 

  91. Fujimoto, Y. et al. Involvement of ACSL in local synthesis of neutral lipids in cytoplasmic lipid droplets in human hepatocyte HuH7. J. Lipid Res. 48, 1280–1292 (2007).

    Article  CAS  PubMed  Google Scholar 

  92. Young, S. G. & Zechner, R. Biochemistry and pathophysiology of intravascular and intracellular lipolysis. Genes Dev. 27, 459–484 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Eichmann, T. O. et al. Studies on the substrate and stereo/regioselectivity of adipose triglyceride lipase, hormone-sensitive lipase, and diacylglycerol-O-acyltransferases. J. Biol. Chem. 287, 41446–41457 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Ouimet, M. & Marcel, Y. L. Regulation of lipid droplet cholesterol efflux from macrophage foam cells. Arterioscler. Thromb. Vasc. Biol. 32, 575–581 (2012).

    Article  CAS  PubMed  Google Scholar 

  95. Ghosh, S., Zhao, B., Bie, J. & Song, J. Macrophage cholesteryl ester mobilization and atherosclerosis. Vascul Pharmacol. 52, 1–10 (2010).

    Article  CAS  PubMed  Google Scholar 

  96. Holm, C., Osterlund, T., Laurell, H. & Contreras, J. A. Molecular mechanisms regulating hormone-sensitive lipase and lipolysis. Annu. Rev. Nutr. 20, 365–393 (2000).

    Article  CAS  PubMed  Google Scholar 

  97. Soni, K. G. et al. Coatomer-dependent protein delivery to lipid droplets. J. Cell Sci. 122, 1834–1841 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Zechner, R., Kienesberger, P. C., Haemmerle, G., Zimmermann, R. & Lass, A. Adipose triglyceride lipase and the lipolytic catabolism of cellular fat stores. J. Lipid Res. 50, 3–21 (2009).

    Article  CAS  PubMed  Google Scholar 

  99. Zimmermann, R., Lass, A., Haemmerle, G. & Zechner, R. Fate of fat: the role of adipose triglyceride lipase in lipolysis. Biochim. Biophys. Acta 1791, 494–500 (2009).

    Article  CAS  PubMed  Google Scholar 

  100. Lass, A., Zimmermann, R., Oberer, M. & Zechner, R. Lipolysis — a highly regulated multi-enzyme complex mediates the catabolism of cellular fat stores. Prog. Lipid Res. 50, 14–27 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Wang, H. et al. Perilipin 5, a lipid droplet-associated protein, provides physical and metabolic linkage to mitochondria. J. Lipid Res. 52, 2159–2168 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Romeo, S. et al. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nature Genet. 40, 1461–1465 (2008).

    Article  CAS  PubMed  Google Scholar 

  103. Murphy, S., Martin, S. & Parton, R. G. Quantitative analysis of lipid droplet fusion: inefficient steady state fusion but rapid stimulation by chemical fusogens. PLoS ONE 5, e15030 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Nakamura, N., Banno, Y. & Tamiya-Koizumi, K. Arf1-dependent PLD1 is localized to oleic acid-induced lipid droplets in NIH3T3 cells. Biochem. Biophys. Res. Commun. 335, 117–123 (2005).

    Article  CAS  PubMed  Google Scholar 

  105. Gubern, A. et al. Lipid droplet biogenesis induced by stress involves triacylglycerol synthesis that depends on group VIA phospholipase A2. J. Biol. Chem. 284, 5697–5708 (2009).

    Article  CAS  PubMed  Google Scholar 

  106. Long, A. P. et al. Lipid droplet de novo formation and fission are linked to the cell cycle in fission yeast. Traffic 13, 705–714 (2012).

    Article  CAS  PubMed  Google Scholar 

  107. Olzmann, J. A., Richter, C. M. & Kopito, R. R. Spatial regulation of UBXD8 and p97/VCP controls ATGL-mediated lipid droplet turnover. Proc. Natl Acad. Sci. USA 110, 1345–1350 (2013).

    Article  PubMed  Google Scholar 

  108. Spandl, J., Lohmann, D., Kuerschner, L., Moessinger, C. & Thiele, C. Ancient ubiquitous protein 1 (AUP1) localizes to lipid droplets and binds the E2 ubiquitin conjugase G2 (Ube2g2) via its G2 binding region. J. Biol. Chem. 286, 5599–5606 (2011).

    Article  CAS  PubMed  Google Scholar 

  109. Klemm, E. J., Spooner, E. & Ploegh, H. L. Dual role of ancient ubiquitous protein 1 (AUP1) in lipid droplet accumulation and endoplasmic reticulum (ER) protein quality control. J. Biol. Chem. 286, 37602–37614 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Singh, R. et al. Autophagy regulates lipid metabolism. Nature 458, 1131–1135 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Thoen, L. F. et al. A role for autophagy during hepatic stellate cell activation. J. Hepatol. 55, 1353–1360 (2011).

    Article  CAS  PubMed  Google Scholar 

  112. Kaushik, S. et al. Autophagy in hypothalamic AgRP neurons regulates food intake and energy balance. Cell. Metab. 14, 173–183 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Hartman, I. Z. et al. Sterol-induced dislocation of 3-hydroxy-3-methylglutaryl coenzyme A reductase from endoplasmic reticulum membranes into the cytosol through a subcellular compartment resembling lipid droplets. J. Biol. Chem. 285, 19288–19298 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Herker, E. et al. Efficient hepatitis C virus particle formation requires diacylglycerol acyltransferase-1. Nature Med. 16, 1295–1298 (2010).

    Article  CAS  PubMed  Google Scholar 

  115. Cornish, K., Wood, D. F. & Windle, J. J. Rubber particles from four different species, examined by transmission electron microscopy and electron-paramagnetic-resonance spin labeling, are found to consist of a homogeneous rubber core enclosed by a contiguous, monolayer biomembrane. Planta 210, 85–96 (1999).

    Article  CAS  PubMed  Google Scholar 

  116. Juengst, C., Klein, M. & Zumbusch, A. Long-term live cell microscopy studies of lipid droplet fusion dynamics in adipocytes. J. Lipid Res. http://dx.doi.org/10.1194/jlr.M042515 (2013).

  117. Beller, M., Thiel, K., Thul, P. J., Jäckle, H. Lipid droplets: a dynamic organelle moves into focus. FEBS Lett. 584, 2176–2182 (2010).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank N. Bremond, F. Wilfling and F. Pincet for critical discussions on the manuscript and G. Howard for editorial assistance. Work on lipid droplets in the Walther and Farese laboratories is supported by the National Institutes of Health (NIH) grants R01GM097194 (to T.C.W.) and RO1GM099844 (to R.V.F). A.R.T. is a fellow of the Marie Curie Budding and Fusion of Lipid Droplets (BFLDs) International Outgoing Fellowships (IOF), within the 7th European Community Framework Program grant to a Partner University Funds exchange grant between the Yale and Ecole Normale Supérieure laboratories.

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Authors and Affiliations

  1. Department of Cell Biology, Yale School of Medicine, 333 Cedar Street, New Haven, 06510, Connecticut, USA

    Abdou Rachid Thiam & Tobias C. Walther

  2. Laboratoire de Physique Statistique, Ecole Normale Supérieure de Paris, Université Pierre et Marie Curie, Université Paris Diderot, Centre National de la Recherche Scientifique, 24 rue Lhomond, Paris, 75005, France

    Abdou Rachid Thiam

  3. Gladstone Institute of Cardiovascular Disease, 1650 Owens Street, San Francisco, 94158, California, USA

    Robert V. Farese Jr

  4. Departments of Medicine and Biochemistry and Biophysics, University of California, San Francisco, 94158, California, USA

    Robert V. Farese Jr

Authors
  1. Abdou Rachid Thiam
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  2. Robert V. Farese Jr
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  3. Tobias C. Walther
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Corresponding authors

Correspondence to Robert V. Farese Jr or Tobias C. Walther.

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Glossary

Critical micellar concentration

The concentration at which surfactants form micelles.

Cosurfactants

Cosurfactants are inefficient surfactants alone and smaller than primary surfactants. They can fill the space between primary surfactants to reduce surface tension. Cosurfactants can easily partition between the different phases.

Surface tension

Surface tension (γ) reflects the energy that is required to increase the surface area of a liquid by a unit area and is the energy cost per unit area generated between two immiscible fluids. The presence of phospholipid surfactants minimizes γ by shielding the interface.

Intrinsic curvature

For a surfactant, it is their spontaneous curvature (dependent on properties such as pH, length of acyl chains and temperature). It reflects the hydrophilic and lipophilic balance of the molecules. If the mean area of the hydrophilic part of a surfactant is larger than that of the hydrophobic part, the curvature of the molecules is considered positive, and it tends to form direct micelles. In the opposite case, the curvature is negative.

Line tension

Line tension (Γ) is the energy cost per unit length at the boundary between different phases. Among many parameters, line tension is a function of surfactant acyl chain length and bending modulus.

Laplace pressure

The pressure difference (ΔP) between the inside and outside of a curved liquid surface. Surface tension compresses the disperse liquid to a spherical shape to minimize the energy of the system. Contraction arrests when a relatively positive Laplace pressure builds up inside the drop.

Permeation

In the context of emulsions it is the process by which one type of molecule (for example, triacylglycerol), which is present in one compartment, crosses a membrane barrier or a liquid film by diffusing through it and thus reaches another compartment.

Dewetting

The rupture of a thin film on a substrate to form a droplet, the counterpart to which is spreading. It depends on the surfactant concentration. Dewetting of an oil droplet within a bilayer occurs when the monolayers of the bilayer wet together. This process can be favoured in emulsions by lowering surface tension.

Contact angle

The contact angle (θ) is the angle at which a liquid interface meets a solid surface. It is also applicable to the angle between an lipid droplet and the endoplasmic reticulum bilayer.

Bending modulus

The bending modulus represents the energy that is needed to bend a monolayer from its spontaneous curvature.

Buckling interface

A 'wrinkled' surface that forms when a monolayer has become rigid because of increased phospholipid density following compression. The wrinkles are a way to relax the applied stress, as they increase the monolayer surface.

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Thiam, A., Farese Jr, R. & Walther, T. The biophysics and cell biology of lipid droplets. Nat Rev Mol Cell Biol 14, 775–786 (2013). https://doi.org/10.1038/nrm3699

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