Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Opinion
  • Published:

Opinion

Lipid droplets: a unified view of a dynamic organelle

Nature Reviews Molecular Cell Biology volume 7, pages 373–378 (2006)Cite this article

Abstract

Lipid droplets form the main lipid store in eukaryotic cells. Although all cells seem to be able to generate lipid droplets, their biogenesis, regulatory mechanisms and interactions with other organelles remain largely elusive. In this article, we outline some of the recent developments in lipid droplet cell biology. We show the mobile and dynamic nature of this organelle, and advocate the adoption of a unified nomenclature to consolidate terminology in this emerging field.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: The formation of lipid droplets.
Figure 2: Lipid droplets in adipocytes.

Similar content being viewed by others

References

  1. Murphy, D. J. The biogenesis and functions of lipid bodies in animals, plants and microorganisms. Prog. Lipid Res. 40, 325–438 (2001).

    Article  CAS  Google Scholar 

  2. Waltermann, M. & Steinbuchel, A. Neutral lipid bodies in prokaryotes: recent insights into structure, formation, and relationship to eukaryotic lipid depots. J. Bacteriol. 187, 3607–3619 (2005).

    Article  Google Scholar 

  3. Martin, S. & Parton, R. G. Caveolin, cholesterol, and lipid bodies. Semin. Cell Dev. Biol. 16, 163–174 (2005).

    Article  CAS  Google Scholar 

  4. Imanishi, Y., Gerke, V. & Palczewski, K. Retinosomes: new insights into intracellular managing of hydrophobic substances in lipid bodies. J. Cell Biol. 166, 447–453 (2004).

    Article  CAS  Google Scholar 

  5. Gross, S. P., Guo, Y., Martinez, J. E. & Welte, M. A. A determinant for directionality of organelle transport in Drosophila embryos. Curr. Biol. 13, 1660–1668 (2003).

    Article  CAS  Google Scholar 

  6. Valetti, C. et al. Role of dynactin in endocytic traffic: effects of dynamitin overexpression and colocalization with CLIP-170. Mol. Biol. Cell 10, 4107–4120 (1999).

    Article  CAS  Google Scholar 

  7. Targett-Adams, P. et al. Live cell analysis and targeting of the lipid droplet-binding adipocyte differentiation-related protein. J. Biol. Chem. 278, 15998–16007 (2003).

    Article  CAS  Google Scholar 

  8. Pol, A. et al. Dynamic and regulated association of caveolin with lipid bodies: modulation of lipid body motility and function by a dominant negative mutant. Mol. Biol. Cell 15, 99–110 (2004).

    Article  CAS  Google Scholar 

  9. 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  Google Scholar 

  10. Blanchette-Mackie, E. J. et al. Perilipin is located on the surface layer of intracellular lipid droplets in adipocytes. J. Lipid Res. 36, 1211–1226 (1995).

    CAS  PubMed  Google Scholar 

  11. Robenek, H. et al. Lipid droplets gain PAT family proteins by interaction with specialized plasma membrane domains. J. Biol. Chem. 280, 26330–26338 (2005).

    Article  CAS  Google Scholar 

  12. Liu, P. et al. Chinese hamster ovary K2 cell lipid droplets appear to be metabolic organelles involved in membrane traffic. J. Biol. Chem. 279, 3787–3792 (2004).

    Article  CAS  Google Scholar 

  13. 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  Google Scholar 

  14. Fujimoto, Y. et al. Identification of major proteins in the lipid droplet-enriched fraction isolated from the human hepatocyte cell line HuH7. Biochim. Biophys. Acta 1644, 47–59 (2004).

    Article  CAS  Google Scholar 

  15. Umlauf, E. et al. Association of stomatin with lipid bodies. J. Biol. Chem. 279, 23699–23709 (2004).

    Article  CAS  Google Scholar 

  16. Tansey, J. T., Sztalryd, C., Hlavin, E. M., Kimmel, A. R. & Londos, C. The central role of perilipin A in lipid metabolism and adipocyte lipolysis. IUBMB Life 56, 379–385 (2004).

    Article  CAS  Google Scholar 

  17. Londos, C., Brasaemle, D. L., Schultz, C. J., Segrest, J. P. & Kimmel, A. R. Perilipins, ADRP, and other proteins that associate with intracellular neutral lipid droplets in animal cells. Semin. Cell Dev. Biol. 10, 51–58 (1999).

    Article  CAS  Google Scholar 

  18. Miura, S. et al. Functional conservation for lipid storage droplet association among perilipin, ADRP, and TIP47 (PAT)-related proteins in mammals, Drosophila, and Dictyostelium. J. Biol. Chem. 277, 32253–32257 (2002).

    Article  CAS  Google Scholar 

  19. 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  Google Scholar 

  20. Tansey, J. T. et al. Perilipin ablation results in a lean mouse with aberrant adipocyte lipolysis, enhanced leptin production, and resistance to diet-induced obesity. Proc. Natl Acad. Sci. USA 98, 6494–6499 (2001).

    Article  CAS  Google Scholar 

  21. Martinez-Botas, J. et al. Absence of perilipin results in leanness and reverses obesity in Lepr db/db mice. Nature Genet. 26, 474–479 (2000).

    Article  CAS  Google Scholar 

  22. Sztalryd, C. et al. Perilipin A is essential for the translocation of hormone-sensitive lipase during lipolytic activation. J. Cell Biol. 161, 1093–1103 (2003).

    Article  CAS  Google Scholar 

  23. Londos, C., Sztalryd, C., Tansey, J. T. & Kimmel, A. R. Role of PAT proteins in lipid metabolism. Biochimie 87, 45–49 (2005).

    Article  CAS  Google Scholar 

  24. Moore, H. P., Silver, R. B., Mottillo, E. P., Bernlohr, D. A. & Granneman, J. G. Perilipin targets a novel pool of lipid droplets for lipolytic attack by hormone-sensitive lipase. J. Biol. Chem. 280, 43109–43120 (2005).

    Article  CAS  Google Scholar 

  25. Tansey, J. T. et al. Functional studies on native and mutated forms of perilipins. A role in protein kinase A-mediated lipolysis of triacylglycerols. J. Biol. Chem. 278, 8401–8406 (2003).

    Article  CAS  Google Scholar 

  26. Serrero, G., Frolov, A., Schroeder, F., Tanaka, K. & Gelhaar, L. Adipose differentiation related protein: expression, purification of recombinant protein in Escherichia coli and characterization of its fatty acid binding properties. Biochim. Biophys. Acta 1488, 245–254 (2000).

    Article  CAS  Google Scholar 

  27. Atshaves, B. P. et al. Sterol carrier protein-2 expression modulates protein and lipid composition of lipid droplets. J. Biol. Chem. 276, 25324–25335 (2001).

    Article  CAS  Google Scholar 

  28. Imamura, M. et al. ADRP stimulates lipid accumulation and lipid droplet formation in murine fibroblasts. Am. J. Physiol. Endocrinol. Metab. 283, E775–E783 (2002).

    Article  CAS  Google Scholar 

  29. Gao, J. & Serrero, G. Adipose differentiation related protein (ADRP) expressed in transfected COS-7 cells selectively stimulates long chain fatty acid uptake. J. Biol. Chem. 274, 16825–16830 (1999).

    Article  CAS  Google Scholar 

  30. Nakamura, N. et al. ADRP is dissociated from lipid droplets by ARF1-dependent mechanism. Biochem. Biophys. Res. Commun. 322, 957–965 (2004).

    Article  CAS  Google Scholar 

  31. Jenkins, G. M. & Frohman, M. A. Phospholipase D: a lipid centric review. Cell. Mol. Life Sci. 62, 2305–2316 (2005).

    Article  CAS  Google Scholar 

  32. 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  Google Scholar 

  33. Marchesan, D. et al. A phospholipase D-dependent process forms lipid droplets containing caveolin, adipocyte differentiation-related protein, and vimentin in a cell-free system. J. Biol. Chem. 278, 27293–27300 (2003).

    Article  CAS  Google Scholar 

  34. Bostrom, P. et al. Cytosolic lipid droplets increase in size by microtubule-dependent complex formation. Arterioscler. Thromb. Vasc. Biol. 25, 1945–1951 (2005).

    Article  Google Scholar 

  35. Zerial, M. & McBride, H. Rab proteins as membrane organizers. Nature Rev. Mol. Cell Biol. 2, 107–117 (2001).

    Article  CAS  Google Scholar 

  36. Ozeki, S. et al. Rab18 localizes to lipid droplets and induces their close apposition to the endoplasmic reticulum-derived membrane. J. Cell Sci. 118, 2601–2611 (2005).

    Article  CAS  Google Scholar 

  37. Martin, S., Driessen, K., Nixon, S. J., Zerial, M. & Parton, R. G. Regulated localization of Rab18 to lipid droplets: effects of lipolytic stimulation and inhibition of lipid droplet catabolism. J. Biol. Chem. 280, 42325–42335 (2005).

    Article  CAS  Google Scholar 

  38. van Manen, H. J., Kraan, Y. M., Roos, D. & Otto, C. Single-cell Raman and fluorescence microscopy reveal the association of lipid bodies with phagosomes in leukocytes. Proc. Natl Acad. Sci. USA 102, 10159–10164 (2005).

    Article  CAS  Google Scholar 

  39. Levine, T. Short-range intracellular trafficking of small molecules across endoplasmic reticulum junctions. Trends Cell Biol. 14, 483–490 (2004).

    Article  CAS  Google Scholar 

  40. Parton, R. G. Caveolae and caveolins. Curr. Opin. Cell Biol. 8, 542–548 (1996).

    Article  CAS  Google Scholar 

  41. Pol, A. et al. A caveolin dominant negative mutant associates with lipid bodies and induces intracellular cholesterol imbalance. J. Cell Biol. 152, 1057–1070 (2001).

    Article  CAS  Google Scholar 

  42. Roy, S. et al. Dominant-negative caveolin inhibits H-Ras function by disrupting cholesterol-rich plasma membrane domains. Nature Cell Biol. 1, 98–105 (1999).

    Article  CAS  Google Scholar 

  43. Fujimoto, T., Kogo, H., Ishiguro, K., Tauchi, K. & Nomura, R. Caveolin-2 is targeted to lipid droplets, a new 'membrane domain' in the cell. J. Cell Biol. 152, 1079–1085 (2001).

    Article  CAS  Google Scholar 

  44. Trigatti, B. L., Anderson, R. G. & Gerber, G. E. Identification of caveolin-1 as a fatty acid binding protein. Biochem. Biophys. Res. Commun. 255, 34–39 (1999).

    Article  CAS  Google Scholar 

  45. Murata, M. et al. VIP21/caveolin is a cholesterol-binding protein. Proc. Natl Acad. Sci. USA 92, 10339–10343 (1995).

    Article  CAS  Google Scholar 

  46. Sharma, D. K. et al. Selective stimulation of caveolar endocytosis by glycosphingolipids and cholesterol. Mol. Biol. Cell 15, 3114–3122 (2004).

    Article  CAS  Google Scholar 

  47. Ost, A., Ortegren, U., Gustavsson, J., Nystrom, F. H. & Stralfors, P. Triacylglycerol is synthesized in a specific subclass of caveolae in primary adipocytes. J. Biol. Chem. 280, 5–8 (2005).

    Article  Google Scholar 

  48. Cohen, A. W. et al. Role of caveolin-1 in the modulation of lipolysis and lipid droplet formation. Diabetes 53, 1261–1270 (2004).

    Article  CAS  Google Scholar 

  49. Zechner, R., Strauss, J. G., Haemmerle, G., Lass, A. & Zimmermann, R. Lipolysis: pathway under construction. Curr. Opin. Lipidol. 16, 333–340 (2005).

    Article  CAS  Google Scholar 

  50. Wang, S. P. et al. The adipose tissue phenotype of hormone-sensitive lipase deficiency in mice. Obes. Res. 9, 119–128 (2001).

    Article  CAS  Google Scholar 

  51. Osuga, J. et al. Targeted disruption of hormone-sensitive lipase results in male sterility and adipocyte hypertrophy, but not in obesity. Proc. Natl Acad. Sci. USA 97, 787–792 (2000).

    Article  CAS  Google Scholar 

  52. Haemmerle, G. et al. Hormone-sensitive lipase deficiency in mice causes diglyceride accumulation in adipose tissue, muscle, and testis. J. Biol. Chem. 277, 4806–4815 (2002).

    Article  CAS  Google Scholar 

  53. Zimmermann, R. et al. Fat mobilization in adipose tissue is promoted by adipose triglyceride lipase. Science 306, 1383–1386 (2004).

    Article  CAS  Google Scholar 

  54. Villena, J. A., Roy, S., Sarkadi-Nagy, E., Kim, K. H. & Sul, H. S. Desnutrin, an adipocyte gene encoding a novel patatin domain-containing protein, is induced by fasting and glucocorticoids: ectopic expression of desnutrin increases triglyceride hydrolysis. J. Biol. Chem. 279, 47066–47075 (2004).

    Article  CAS  Google Scholar 

  55. Jenkins, C. M. et al. Identification, cloning, expression, and purification of three novel human calcium-independent phospholipase A2 family members possessing triacylglycerol lipase and acylglycerol transacylase activities. J. Biol. Chem. 279, 48968–48975 (2004).

    Article  CAS  Google Scholar 

  56. Hope, R. G., Murphy, D. J. & McLauchlan, J. The domains required to direct core proteins of hepatitis C virus and GB virus-B to lipid droplets share common features with plant oleosin proteins. J. Biol. Chem. 277, 4261–4270 (2002).

    Article  CAS  Google Scholar 

  57. Ting, J. T., Balsamo, R. A., Ratnayake, C. & Huang, A. H. Oleosin of plant seed oil bodies is correctly targeted to the lipid bodies in transformed yeast. J. Biol. Chem. 272, 3699–3706 (1997).

    Article  CAS  Google Scholar 

  58. Shimano, H. Sterol regulatory element-binding proteins (SREBPs): transcriptional regulators of lipid synthetic genes. Prog. Lipid Res. 40, 439–452 (2001).

    Article  CAS  Google Scholar 

  59. Li, Y. et al. Enrichment of endoplasmic reticulum with cholesterol inhibits sarcoplasmic-endoplasmic reticulum calcium ATPase-2b activity in parallel with increased order of membrane lipids: implications for depletion of endoplasmic reticulum calcium stores and apoptosis in cholesterol-loaded macrophages. J. Biol. Chem. 279, 37030–37039 (2004).

    Article  CAS  Google Scholar 

  60. Feng, B. et al. The endoplasmic reticulum is the site of cholesterol-induced cytotoxicity in macrophages. Nature Cell Biol. 5, 781–792 (2003).

    Article  CAS  Google Scholar 

  61. Welte, M. A. et al. Regulation of lipid-droplet transport by the perilipin homolog LSD2. Curr. Biol. 15, 1266–1275 (2005).

    Article  CAS  Google Scholar 

  62. Gronke, S. et al. Control of fat storage by a Drosophila PAT domain protein. Curr. Biol. 13, 603–606 (2003).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors acknowledge the support of the National Health and Medical Research Council of Australia and the National Institutes of Health, USA. We are extremely grateful to D. Brasaemle, D. Brown, T. Fujimoto, C. Londos, A. Pol, I. Tabas, J. Whitehead and many other colleagues for invaluable discussions on nomenclature during the preparation of this manuscript. We also thank C. Ferguson for assistance with electron microscopy.

Author information

Authors and Affiliations

  1. the Institute for Molecular Bioscience, and Centre for Microscopy and Microanalysis, University of Queensland, Brisbane, QLD 4072, Australia

    Sally Martin & Robert G. Parton

Authors
  1. Sally Martin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Robert G. Parton
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Robert G. Parton.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Related links

Related links

FURTHER INFORMATION

A movie of lipid droplet formation from the American Society for Cell Biology

Rights and permissions

Reprints and permissions

About this article

Cite this article

Martin, S., Parton, R. Lipid droplets: a unified view of a dynamic organelle. Nat Rev Mol Cell Biol 7, 373–378 (2006). https://doi.org/10.1038/nrm1912

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrm1912

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing