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Dynamics and functions of lipid droplets

Nature Reviews Molecular Cell Biology volume 20, pages 137–155 (2019)Cite this article

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Abstract

Lipid droplets are storage organelles at the centre of lipid and energy homeostasis. They have a unique architecture consisting of a hydrophobic core of neutral lipids, which is enclosed by a phospholipid monolayer that is decorated by a specific set of proteins. Originating from the endoplasmic reticulum, lipid droplets can associate with most other cellular organelles through membrane contact sites. It is becoming apparent that these contacts between lipid droplets and other organelles are highly dynamic and coupled to the cycles of lipid droplet expansion and shrinkage. Importantly, lipid droplet biogenesis and degradation, as well as their interactions with other organelles, are tightly coupled to cellular metabolism and are critical to buffer the levels of toxic lipid species. Thus, lipid droplets facilitate the coordination and communication between different organelles and act as vital hubs of cellular metabolism.

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Fig. 1: Steps in lipid droplet biogenesis.
Fig. 2: Mechanisms of lipid droplet protein targeting and degradation.
Fig. 3: Lipid droplet–organelle contacts.
Fig. 4: Lipid droplets as buffers against stress.

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Acknowledgements

The authors apologize to all scientists whose important contributions were not referenced in this review owing to space limitations. The authors thank Z. Li and L. Krshnan for careful reading and discussion of the manuscript. J.A.O. acknowledges funding from the US National Institutes of Health (R01GM112948 and R21AG056502) and the American Heart Association (16GRNT30870005). P.C. acknowledges funding from the European Research Council (starting grant DropFat 309477) and the Wellcome Trust.

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Nature Reviews Molecular Cell Biology thanks D. Mashek, S. Cohen and J. Goodman for their contribution to the peer review of this work.

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Authors and Affiliations

  1. Department of Nutritional Sciences and Toxicology, University of California–Berkeley, Berkeley, CA, USA

    James A. Olzmann

  2. Sir William Dunn School of Pathology, University of Oxford, Oxford, UK

    Pedro Carvalho

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Glossary

Lipotoxicity

Deleterious effects of improperly stored lipids on cellular health.

COPII

Complex of proteins that coat vesicles budding from endoplasmic reticulum (ER) exit sites and facilitate anterograde protein transport towards the Golgi.

Phospholipid scramblases

Proteins that mediate the bidirectional exchange of phospholipids between two leaflets of a lipid bilayer.

Perilipins

Family of proteins that coat lipid droplets and regulate lipid droplet stability and turnover.

COPI coatomer complex

Complex of proteins that coat vesicles budding from the Golgi and facilitate retrograde protein transport.

Polytopic membrane proteins

Membrane-embedded proteins in which the polypeptide chain crosses the membrane multiple times.

Farnesylation

Post-translational modification of a protein by addition of an isoprenoid farnesyl group to a cysteine residue.

ER-associated protein degradation

(ERAD). A process that mediates the recognition and delivery of aberrant (for example, misfolded) proteins from the endoplasmic reticulum to the proteasome for degradation.

Packing defects

Regions in which the neutral lipid or the hydrocarbon chains of phospholipids are exposed to the aqueous cytoplasm.

SNAREs

Family of proteins that mediate membrane fusion.

Brown adipocytes

Type of adipocyte that contains large numbers of mitochondria and expresses high amounts of uncoupling protein 1, resulting in the dissipation of the proton motive force and generation of heat.

Insulin resistance

Condition in which cells fail to respond appropriately to insulin.

Peroxidative damage

A form of oxidative damage, such as the formation of lipid peroxides.

Ferroptosis

Regulated, iron-dependent form of cell death that is characterized by the accumulation of lipid peroxides.

Apolipoprotein

Lipid-binding protein that enables lipid transport throughout the body.

Retrotranslocation

Movement of endoplasmic reticulum-associated protein degradation substrates across the endoplasmic reticulum membrane back into the cytoplasm for degradation by the proteasome.

Fatty acid oxidation diseases

Heterogeneous group of rare, autosomal recessive diseases characterized by defects in fatty acid catabolism.

Ichthyosis

Condition characterized by skin that is thickened, dry and scaly.

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Olzmann, J.A., Carvalho, P. Dynamics and functions of lipid droplets. Nat Rev Mol Cell Biol 20, 137–155 (2019). https://doi.org/10.1038/s41580-018-0085-z

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