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.
This is a preview of subscription content, access via your institution
Open Access articles citing this article.
Molecular and Cellular Pediatrics Open Access 22 October 2021
Scientific Reports Open Access 29 September 2021
Subscribe to Journal
Get full journal access for 1 year
only $8.25 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Get time limited or full article access on ReadCube.
All prices are NET prices.
van Meer, G. Cellular lipidomics. EMBO J. 24, 3159–3165 (2005).
Yetukuri, L., Ekroos, K., Vidal-Puig, A. & Oresic, M. Informatics and computational strategies for the study of lipids. Mol. Biosyst. 4, 121–127 (2008).
Dennis, E. A. Lipidomics joins the omics evolution. Proc. Natl Acad. Sci. USA 106, 2089–2090 (2009).
Wenk, M. R. The emerging field of lipidomics. Nature Rev. Drug Discov. 4, 594–610 (2005).
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).
Luzzati, V. Biological significance of lipid polymorphism: the cubic phases. Curr. Opin. Struct. Biol. 7, 661–668 (1997).
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).
Poulsen, L. R., Lopez-Marques, R. L. & Palmgren, M. G. Flippases: still more questions than answers. Cell. Mol. Life Sci. 65, 3119–3125 (2008).
Simons, K. & van Meer, G. Lipid sorting in epithelial cells. Biochemistry 27, 6197–6202 (1988).
Lingwood, D. & Simons, K. Lipid rafts as a membrane-organizing principle. Science 327, 46–50 (2010).
Zech, T. et al. Accumulation of raft lipids in T-cell plasma membrane domains engaged in TCR signalling. EMBO J. 28, 466–476 (2009).
Hunte, C. & Richers, S. Lipids and membrane protein structures. Curr. Opin. Struct. Biol. 18, 406–411 (2008).
Murata, M. et al. VIP21/caveolin is a cholesterol-binding protein. Proc. Natl Acad. Sci. USA 92, 10339–10343 (1995).
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).
Allende, M. L. & Proia, R. L. Lubricating cell signaling pathways with gangliosides. Curr. Opin. Struct. Biol. 12, 587–592 (2002).
Haberkant, P. et al. Protein-sphingolipid interactions within cellular membranes. J. Lipid Res. 49, 251–262 (2008).
Postle, A. D. & Hunt, A. N. Dynamic lipidomics with stable isotope labelling. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 877, 2716–2721 (2009).
Bretscher, M. S. & Munro, S. Cholesterol and the Golgi apparatus. Science 261, 1280–1281 (1993).
Brugger, B. et al. Evidence for segregation of sphingomyelin and cholesterol during formation of COPI-coated vesicles. J. Cell Biol. 151, 507–518 (2000).
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).
Behnia, R. & Munro, S. Organelle identity and the signposts for membrane traffic. Nature 438, 597–604 (2005).
Di Paolo, G. & De Camilli, P. Phosphoinositides in cell regulation and membrane dynamics. Nature 443, 651–657 (2006).
Wenk, M. R. et al. Phosphoinositide profiling in complex lipid mixtures using electrospray ionization mass spectrometry. Nature Biotech. 21, 813–817 (2003).
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).
Brown, M. S. & Goldstein, J. L. Cholesterol feedback: from Schoenheimer's bottle to Scap's MELADL. J. Lipid Res. 50, S15–S27 (2009).
Guan, X. L. et al. Functional interactions between sphingolipids and sterols in biological membranes regulating cell physiology. Mol. Biol. Cell 20, 2083–2095 (2009).
Mesmin, B. & Maxfield, F. R. Intracellular sterol dynamics. Biochim. Biophys. Acta 1791, 636–645 (2009).
Veatch, S. L. et al. Critical fluctuations in plasma membrane vesicles. ACS Chem. Biol. 3, 287–293 (2008).
Kuerschner, L. et al. Polyene-lipids: a new tool to image lipids. Nature Methods 2, 39–45 (2005).
Neef, A. B. & Schultz, C. Selective fluorescence labeling of lipids in living cells. Angew. Chem. Int. Ed. Engl. 48, 1498–1500 (2009).
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).
Ejsing, C. S. et al. Automated identification and quantification of glycerophospholipid molecular species by multiple precursor ion scanning. Anal. Chem. 78, 6202–6214 (2006).
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).
Schmelzer, K., Fahy, E., Subramaniam, S. & Dennis, E. A. The lipid maps initiative in lipidomics. Methods Enzymol. 432, 171–183 (2007).
Makarov, A. et al. Performance evaluation of a hybrid linear ion trap/orbitrap mass spectrometer. Anal. Chem. 78, 2113–2120 (2006).
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).
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).
Takamori, S. et al. Molecular anatomy of a trafficking organelle. Cell 127, 831–846 (2006).
Kito, K. & Ito, T. Mass spectrometry-based approaches toward absolute quantitative proteomics. Curr. Genomics 9, 263–274 (2008).
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).
Seeberger, P. H. & Werz, D. B. Synthesis and medical applications of oligosaccharides. Nature 446, 1046–1051 (2007).
Vartiainen, E. et al. Thirty-five-year trends in cardiovascular risk factors in Finland. Int. J. Epidemiol. 39, 504–518 (2009).
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).
Graessler, J. et al. Top-down lipidomics reveals ether lipid deficiency in blood plasma of hypertensive patients. PLoS One 4, e6261 (2009).
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).
Oresic, M., Hanninen, V. A. & Vidal-Puig, A. Lipidomics: a new window to biomedical frontiers. Trends Biotechnol. 26, 647–652 (2008).
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).
Oresic, M. Metabolomics, a novel tool for studies of nutrition, metabolism and lipid dysfunction. Nutr. Metab. Cardiovasc. Dis. 19, 816–824 (2009).
Han, X. Neurolipidomics: challenges and developments. Front. Biosci. 12, 2601–2615 (2007).
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).
Glish, G. L. & Burinsky, D. J. Hybrid mass spectrometers for tandem mass spectrometry. J. Am. Soc. Mass Spectrom. 19, 161–172 (2008).
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).
Bligh, E. G. & Dyer, W. J. A rapid method of total lipid extraction and purification. Can. J. Biochem. Physiol. 37, 911–917 (1959).
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).
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).
Wang, Y. et al. Targeted lipidomic analysis of oxysterols in the embryonic central nervous system. Mol. Biosyst 5, 529–541 (2009).
Griffiths, W. J. & Wang, Y. Mass spectrometry: from proteomics to metabolomics and lipidomics. Chem. Soc. Rev. 38, 1882–1896 (2009).
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).
Schwudke, D. et al. Top-down lipidomic screens by multivariate analysis of high-resolution survey mass spectra. Anal. Chem. 79, 4083–4093 (2007).
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).
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.
Kai Simons is a co-founder of the biotechnology company JADO technologies, which specializes in membrane invention technologies including lipid raft modulation.
About this article
Cite this article
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
This article is cited by
The Journal of Membrane Biology (2022)
A Review of Mechanics-Based Mesoscopic Membrane Remodeling Methods: Capturing Both the Physics and the Chemical Diversity
The Journal of Membrane Biology (2022)
Journal of Ocean University of China (2022)
Nature Methods (2022)
Molecular and Cellular Pediatrics (2021)