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Membrane lipids: where they are and how they behave

Key Points

  • Lipids function as essential structural components of membranes, as signalling molecules, as chemical identifiers of specific membranes and as energy storage molecules. The synthesis of lipids is non-uniformly distributed among a few cellular membranes, which requires most organelles to depend on lipid transport processes to achieve their full complement of lipids.

  • Organelles differ both quantitatively and qualitatively in their lipid content. In many organelles, the lipid composition of separate leaflets of the membrane bilayer is significantly different, which produces asymmetry across the bilayer — a situation that is maintained by ATP-dependent flippases.

  • Lipid transport between and within organelles is poorly understood, but a growing number of genes that are involved in these processes have been unambiguously identified, and their mechanisms of action are under active investigation. There is clear evidence that several lipids are transported between organelles by non-vesicular mechanisms that involve zones of apposition between donor and acceptor compartments, and macromolecular assemblies that involve multiple lipids and proteins.

  • Several dozen lipids participate in intra- and intercellular signalling processes. In most instances, the levels of signalling molecules are exceedingly low compared with the complement of structural lipids that is present in membranes.

  • Lipids adopt defined phases depending on their molecular structure and the physical conditions. In lipid mixtures, two fluid phases can coexist with different physical properties: liquid-disordered and liquid-ordered.

  • Liquid-ordered assemblies in biomembranes, known as lipid rafts, are small and transient but can coalesce and become stabilized during signalling and vesicle budding. How proteins contribute to phase separation and preferentially distribute into one of the two different phases (or at their interface) is presently unclear.


Throughout the biological world, a 30 Å hydrophobic film typically delimits the environments that serve as the margin between life and death for individual cells. Biochemical and biophysical findings have provided a detailed model of the composition and structure of membranes, which includes levels of dynamic organization both across the lipid bilayer (lipid asymmetry) and in the lateral dimension (lipid domains) of membranes. How do cells apply anabolic and catabolic enzymes, translocases and transporters, plus the intrinsic physical phase behaviour of lipids and their interactions with membrane proteins, to create the unique compositions and multiple functionalities of their individual membranes?

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Figure 1: Membrane lipids and lipid second messengers.
Figure 2: Lipid synthesis and steady-state composition of cell membranes.
Figure 3: Mechanisms for generating asymmetric lipid distribution.
Figure 4: Emerging models for lipid transport.


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A family of storage lipids consisting of glycerol esterified to three fatty acids, forming the hydrophobic core of lipid droplets and blood lipoproteins together with steryl esters.

Steryl ester

A family of storage lipids consisting of sterol esterified to one fatty acid, forming the hydrophobic core of lipid droplets and blood lipoproteins together with triacylglycerol molecules.


The characteristic of being polar on one side of the molecule and apolar on the opposite side.

Lysosomal hydrolase

An enzyme that hydrolyses biomolecules in lysosomes.


A family of long-chain, unsaturated and methylated hydrocarbons that consist of varying numbers of isoprene units that terminate in an α-saturated isoprenoid group and contain an alcohol functional group. Dolicholphosphate and dolicholpyrophosphate anchor sugar molecules to the ER membrane for transfer to proteins in the ER lumen.

Multivesicular body

An endosome containing internal vesicles that originate from inward budding. This direction of budding is away from the cytosol (opposite to the regular budding of transport vesicles) and a different molecular machinery has been found to be responsible.

P-type ATPase

One of a family of membrane-embedded transporters that share a phosphorylated intermediate as part of their reaction cycle. It includes the Ca2+- and Na+/K+-ATPases and the P4 family of lipid flippases.


A mechanism (involving incompletely characterized components) that allows transmembrane movement of lipids and relaxation of lipid asymmetry on cell stimulation.


The coat protein of caveolae. It is anchored by a hydrophobic loop and 1–3 palmitoylated cysteines. Caveolin interacts with cholesterol and oligomerizes.

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

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