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The functional universe of membrane contact sites

Nature Reviews Molecular Cell Biology volume 21, pages 7–24 (2020)Cite this article

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Abstract

Organelles compartmentalize eukaryotic cells, enhancing their ability to respond to environmental and developmental changes. One way in which organelles communicate and integrate their activities is by forming close contacts, often called ‘membrane contact sites’ (MCSs). Interest in MCSs has grown dramatically in the past decade as it is has become clear that they are ubiquitous and have a much broader range of critical roles in cells than was initially thought. Indeed, functions for MCSs in intracellular signalling (particularly calcium signalling, reactive oxygen species signalling and lipid signalling), autophagy, lipid metabolism, membrane dynamics, cellular stress responses and organelle trafficking and biogenesis have now been reported.

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Fig. 1: Functions of membrane contact sites.
Fig. 2: Diversity of membrane contact sites.
Fig. 3: Phosphoinositide metabolism at membrane contact sites.
Fig. 4: Calcium signalling and signalling in trans at membrane contact sites.
Fig. 5: Examples of autophagy at membrane contact sites.
Fig. 6: Roles of membrane contact sites in cellular stress responses.

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Acknowledgements

This work was supported by the Intramural Research Program of the US National Institute of Diabetes and Digestive and Kidney Diseases. The authors thank Mary Weston for critically reading the manuscript.

Author information

Authors and Affiliations

  1. National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA

    William A. Prinz & Alexandre Toulmay

  2. National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA

    Tamas Balla

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  1. William A. Prinz
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The authors contributed equally to all aspects of the article.

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Correspondence to William A. Prinz.

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Glossary

Multivesicular bodies

(MVBs). Endocytic compartments containing internal luminal vesicles.

Store-operated calcium entry

The regulated entry of Ca2+ into cells in response to the depletion of Ca2+ in the endoplasmic reticulum.

ER stress

An accumulation of unfolded proteins in the endoplasmic reticulum (ER) that affects ER function.

Ceramides

Lipids used to generate complex sphingolipids, one of the major types of lipid in cellular membranes.

Phosphatidylinositol kinases

Kinases that phosphorylate phosphatidylinositol on the inositol moiety.

Inositol 1,4,5-trisphosphate receptors

(IP3Rs). Endoplasmic Ca2+ channels activated by inositol 1,4,5-trisphosphate, an important signalling molecule formed by the cleavage of phosphatidylinositol 4,5-bisphosphate.

ER–mitochondria encounter structure

(ERMES). An endoplasmic reticulum (ER)–mitochondrial tethering complex found in yeasts.

Sphingolipids

A major type of lipids found in cellular membranes.

Septins

A group of GTP-binding proteins that can assemble into cytoskeletal-like structures.

Interscapular

The region between the shoulder blades.

Brown adipose tissue

A type of adipose tissue that serves as a site of thermogenesis.

Galactoglycerolipids

A family of glycerolipids that contain one or more sugars linked directly to the glycerol moiety.

Selective autophagy

A degradative pathway in which particular organelles or aggregates are degraded in lysosomes and vacuoles in development and in response to nutrient stress.

Unfolded protein response

Stress response pathways induced by endoplasmic reticulum stress.

TDP-43

TAR DNA-binding protein 43 (TDP-43) is a 43-kDa RNA and DNA-binding protein that is pathologically linked to amyotrophic lateral sclerosis and frontotemporal dementia.

Presenilin

A membrane protein thought to contribute to the development of Alzheimer disease.

Chorea-acanthocytosis

A rare neurological disorder that affects body movement.

α-Synuclein

A protein predominantly expressed in neurons that can cluster into insoluble aggregates in Parkinson disease and other neurogenerative disorders.

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Prinz, W.A., Toulmay, A. & Balla, T. The functional universe of membrane contact sites. Nat Rev Mol Cell Biol 21, 7–24 (2020). https://doi.org/10.1038/s41580-019-0180-9

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