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Lipidomics: coming to grips with lipid diversity

Abstract

Although lipids are biomolecules with seemingly simple chemical structures, the molecular composition of the cellular lipidome is complex and, currently, poorly understood. The exact mechanisms of how compositional complexity affects cell homeostasis and its regulation also remain unclear. This emerging field is developing sensitive mass spectrometry technologies for the quantitative characterization of the lipidome. Here, we argue that lipidomics will become an essential tool kit in cell and developmental biology, molecular medicine and nutrition.

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Figure 1: The molecular diversity of lipid species.
Figure 2: Analytical technologies for understanding the lipidome molecular complexity.

References

  1. 1

    van Meer, G. Cellular lipidomics. EMBO J. 24, 3159–3165 (2005).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  2. 2

    Yetukuri, L., Ekroos, K., Vidal-Puig, A. & Oresic, M. Informatics and computational strategies for the study of lipids. Mol. Biosyst. 4, 121–127 (2008).

    CAS  Article  Google Scholar 

  3. 3

    Dennis, E. A. Lipidomics joins the omics evolution. Proc. Natl Acad. Sci. USA 106, 2089–2090 (2009).

    CAS  Article  Google Scholar 

  4. 4

    Wenk, M. R. The emerging field of lipidomics. Nature Rev. Drug Discov. 4, 594–610 (2005).

    CAS  Article  Google Scholar 

  5. 5

    Almsherqi, Z. A., Kohlwein, S. D. & Deng, Y. Cubic membranes: a legend beyond the Flatland* of cell membrane organization. J. Cell Biol. 173, 839–844 (2006).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  6. 6

    Luzzati, V. Biological significance of lipid polymorphism: the cubic phases. Curr. Opin. Struct. Biol. 7, 661–668 (1997).

    CAS  Article  Google Scholar 

  7. 7

    van Meer, G., Voelker, D. R. & Feigenson, G. W. Membrane lipids: where they are and how they behave. Nature Rev. Mol. Cell Biol. 9, 112–124 (2008).

    CAS  Article  Google Scholar 

  8. 8

    Poulsen, L. R., Lopez-Marques, R. L. & Palmgren, M. G. Flippases: still more questions than answers. Cell. Mol. Life Sci. 65, 3119–3125 (2008).

    CAS  Article  Google Scholar 

  9. 9

    Simons, K. & van Meer, G. Lipid sorting in epithelial cells. Biochemistry 27, 6197–6202 (1988).

    CAS  Article  Google Scholar 

  10. 10

    Lingwood, D. & Simons, K. Lipid rafts as a membrane-organizing principle. Science 327, 46–50 (2010).

    CAS  Article  Google Scholar 

  11. 11

    Zech, T. et al. Accumulation of raft lipids in T-cell plasma membrane domains engaged in TCR signalling. EMBO J. 28, 466–476 (2009).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  12. 12

    Hunte, C. & Richers, S. Lipids and membrane protein structures. Curr. Opin. Struct. Biol. 18, 406–411 (2008).

    CAS  Article  Google Scholar 

  13. 13

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

    CAS  Article  PubMed  Google Scholar 

  14. 14

    Hanson, M. A. et al. A specific cholesterol binding site is established by the 2.8 Å structure of the human β2-adrenergic receptor. Structure 16, 897–905 (2008).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  15. 15

    Allende, M. L. & Proia, R. L. Lubricating cell signaling pathways with gangliosides. Curr. Opin. Struct. Biol. 12, 587–592 (2002).

    CAS  Article  Google Scholar 

  16. 16

    Haberkant, P. et al. Protein-sphingolipid interactions within cellular membranes. J. Lipid Res. 49, 251–262 (2008).

    CAS  Article  Google Scholar 

  17. 17

    Postle, A. D. & Hunt, A. N. Dynamic lipidomics with stable isotope labelling. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 877, 2716–2721 (2009).

    CAS  Article  Google Scholar 

  18. 18

    Bretscher, M. S. & Munro, S. Cholesterol and the Golgi apparatus. Science 261, 1280–1281 (1993).

    CAS  Article  Google Scholar 

  19. 19

    Brugger, B. et al. Evidence for segregation of sphingomyelin and cholesterol during formation of COPI-coated vesicles. J. Cell Biol. 151, 507–518 (2000).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  20. 20

    Klemm, R. W. et al. Segregation of sphingolipids and sterols during formation of secretory vesicles at the trans-Golgi network. J. Cell Biol. 185, 601–612 (2009).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  21. 21

    Behnia, R. & Munro, S. Organelle identity and the signposts for membrane traffic. Nature 438, 597–604 (2005).

    CAS  Article  Google Scholar 

  22. 22

    Di Paolo, G. & De Camilli, P. Phosphoinositides in cell regulation and membrane dynamics. Nature 443, 651–657 (2006).

    CAS  Article  Google Scholar 

  23. 23

    Wenk, M. R. et al. Phosphoinositide profiling in complex lipid mixtures using electrospray ionization mass spectrometry. Nature Biotech. 21, 813–817 (2003).

    CAS  Article  Google Scholar 

  24. 24

    Pettitt, T. R., Dove, S. K., Lubben, A., Calaminus, S. D. & Wakelam, M. J. Analysis of intact phosphoinositides in biological samples. J. Lipid Res. 47, 1588–1596 (2006).

    CAS  Article  Google Scholar 

  25. 25

    Brown, M. S. & Goldstein, J. L. Cholesterol feedback: from Schoenheimer's bottle to Scap's MELADL. J. Lipid Res. 50, S15–S27 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  26. 26

    Guan, X. L. et al. Functional interactions between sphingolipids and sterols in biological membranes regulating cell physiology. Mol. Biol. Cell 20, 2083–2095 (2009).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  27. 27

    Mesmin, B. & Maxfield, F. R. Intracellular sterol dynamics. Biochim. Biophys. Acta 1791, 636–645 (2009).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  28. 28

    Veatch, S. L. et al. Critical fluctuations in plasma membrane vesicles. ACS Chem. Biol. 3, 287–293 (2008).

    CAS  Article  Google Scholar 

  29. 29

    Kuerschner, L. et al. Polyene-lipids: a new tool to image lipids. Nature Methods 2, 39–45 (2005).

    CAS  Article  Google Scholar 

  30. 30

    Neef, A. B. & Schultz, C. Selective fluorescence labeling of lipids in living cells. Angew. Chem. Int. Ed. Engl. 48, 1498–1500 (2009).

    CAS  Article  Google Scholar 

  31. 31

    Burnum, K. E. et al. Spatial and temporal alterations of phospholipids determined by mass spectrometry during mouse embryo implantation. J. Lipid Res. 50, 2290–2298 (2009).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  32. 32

    Ejsing, C. S. et al. Automated identification and quantification of glycerophospholipid molecular species by multiple precursor ion scanning. Anal. Chem. 78, 6202–6214 (2006).

    CAS  Article  Google Scholar 

  33. 33

    Ejsing, C. S. et al. Global analysis of the yeast lipidome by quantitative shotgun mass spectrometry. Proc. Natl Acad. Sci. USA 106, 2136–2141 (2009).

    CAS  Article  Google Scholar 

  34. 34

    Schmelzer, K., Fahy, E., Subramaniam, S. & Dennis, E. A. The lipid maps initiative in lipidomics. Methods Enzymol. 432, 171–183 (2007).

    CAS  Article  Google Scholar 

  35. 35

    Makarov, A. et al. Performance evaluation of a hybrid linear ion trap/orbitrap mass spectrometer. Anal. Chem. 78, 2113–2120 (2006).

    CAS  Article  Google Scholar 

  36. 36

    Kalvodova, L. et al. The lipidomes of vesicular stomatitis virus, semliki forest virus, and the host plasma membrane analyzed by quantitative shotgun mass spectrometry. J. Virol. 83, 7996–8003 (2009).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  37. 37

    Niemela, P. S., Castillo, S., Sysi-Aho, M. & Oresic, M. Bioinformatics and computational methods for lipidomics. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 877, 2855–2862 (2009).

    Article  Google Scholar 

  38. 38

    Takamori, S. et al. Molecular anatomy of a trafficking organelle. Cell 127, 831–846 (2006).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  39. 39

    Kito, K. & Ito, T. Mass spectrometry-based approaches toward absolute quantitative proteomics. Curr. Genomics 9, 263–274 (2008).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  40. 40

    Moore, J. D., Caufield, W. V. & Shaw, W. A. Quantitation and standardization of lipid internal standards for mass spectroscopy. Methods Enzymol. 432, 351–367 (2007).

    CAS  Article  Google Scholar 

  41. 41

    Seeberger, P. H. & Werz, D. B. Synthesis and medical applications of oligosaccharides. Nature 446, 1046–1051 (2007).

    CAS  Article  Google Scholar 

  42. 42

    Vartiainen, E. et al. Thirty-five-year trends in cardiovascular risk factors in Finland. Int. J. Epidemiol. 39, 504–518 (2009).

    Article  Google Scholar 

  43. 43

    Beilin, L. J., Burke, V., Puddey, I. B., Mori, T. A. & Hodgson, J. M. Recent developments concerning diet and hypertension. Clin. Exp. Pharmacol. Physiol. 28, 1078–1082 (2001).

    CAS  Article  Google Scholar 

  44. 44

    Graessler, J. et al. Top-down lipidomics reveals ether lipid deficiency in blood plasma of hypertensive patients. PLoS One 4, e6261 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  45. 45

    Pietilainen, K. H. et al. Acquired obesity is associated with changes in the serum lipidomic profile independent of genetic effects — a monozygotic twin study. PLoS ONE 2, e218 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  46. 46

    Oresic, M., Hanninen, V. A. & Vidal-Puig, A. Lipidomics: a new window to biomedical frontiers. Trends Biotechnol. 26, 647–652 (2008).

    CAS  Article  Google Scholar 

  47. 47

    Leidl, K., Liebisch, G., Richter, D. & Schmitz, G. Mass spectrometric analysis of lipid species of human circulating blood cells. Biochim. Biophys. Acta 1781, 655–664 (2008).

    CAS  Article  Google Scholar 

  48. 48

    Oresic, M. Metabolomics, a novel tool for studies of nutrition, metabolism and lipid dysfunction. Nutr. Metab. Cardiovasc. Dis. 19, 816–824 (2009).

    CAS  Article  Google Scholar 

  49. 49

    Han, X. Neurolipidomics: challenges and developments. Front. Biosci. 12, 2601–2615 (2007).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  50. 50

    Ridenour, W. B., Kliman, M., McLean, J. A. & Caprioli, R. M. Structural characterization of phospholipids and peptides directly from tissue sections by MALDI traveling-wave ion mobility-mass spectrometry. Anal. Chem. 82, 1881–1889 (2010).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  51. 51

    Glish, G. L. & Burinsky, D. J. Hybrid mass spectrometers for tandem mass spectrometry. J. Am. Soc. Mass Spectrom. 19, 161–172 (2008).

    CAS  Article  Google Scholar 

  52. 52

    Ekroos, K. et al. Charting molecular composition of phosphatidylcholines by fatty acid scanning and ion trap MS3 fragmentation. J. Lipid Res. 44, 2181–2192 (2003).

    CAS  Article  Google Scholar 

  53. 53

    Bligh, E. G. & Dyer, W. J. A rapid method of total lipid extraction and purification. Can. J. Biochem. Physiol. 37, 911–917 (1959).

    CAS  Article  Google Scholar 

  54. 54

    Folch, J. M., Lees, M., Sloane-Stanley, G. H. A simple method for the isolation and purification of total lipids from animal tissue. J. Biol. Chem. 226, 497–509 (1957).

    CAS  PubMed  Google Scholar 

  55. 55

    Matyash, V., Liebisch, G., Kurzchalia, T. V., Shevchenko, A. & Schwudke, D. Lipid extraction by methyl-tert-butyl ether for high-throughput lipidomics. J. Lipid Res. 49, 1137–1146 (2008).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  56. 56

    Wang, Y. et al. Targeted lipidomic analysis of oxysterols in the embryonic central nervous system. Mol. Biosyst 5, 529–541 (2009).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  57. 57

    Griffiths, W. J. & Wang, Y. Mass spectrometry: from proteomics to metabolomics and lipidomics. Chem. Soc. Rev. 38, 1882–1896 (2009).

    CAS  Article  Google Scholar 

  58. 58

    Ivanova, P. T., Milne, S. B., Myers, D. S. & Brown, H. A. Lipidomics: a mass spectrometry based systems level analysis of cellular lipids. Curr. Opin. Chem. Biol. 13, 526–531 (2009).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  59. 59

    Schwudke, D. et al. Top-down lipidomic screens by multivariate analysis of high-resolution survey mass spectra. Anal. Chem. 79, 4083–4093 (2007).

    CAS  Article  Google Scholar 

  60. 60

    Han, X. & Gross, R. W. Shotgun lipidomics: electrospray ionization mass spectrometric analysis and quantitation of cellular lipidomes directly from crude extracts of biological samples. Mass Spectrom. Rev. 24, 367–412 (2005).

    CAS  Article  Google Scholar 

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Acknowledgements

Work in the K.S. laboratory was supported by EUFP6 PRISM grant LSHB-CT2007–037,740, DFG Schwerpunktprogramm1175, BMBF BioChance Plus grant 0313,827 and BMBF ForMaT grant 03FO1212. Work in the A.S. laboratory was supported by DFG SFB TRR 83 grant.

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Correspondence to Kai Simons.

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Kai Simons is a co-founder of the biotechnology company JADO technologies, which specializes in membrane invention technologies including lipid raft modulation.

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Shevchenko, A., Simons, K. Lipidomics: coming to grips with lipid diversity. Nat Rev Mol Cell Biol 11, 593–598 (2010). https://doi.org/10.1038/nrm2934

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