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Endoplasmic reticulum–mitochondria contacts: function of the junction

Key Points

  • The endoplasmic reticulum (ER) forms contacts with several organelles, and the most well-characterized of these are ER–mitochondria contacts. Regions of close contact between the ER and mitochondrial membranes can be observed by electron microscopy and fluorescence microscopy in animal cells and yeast.

  • The distance between the ER and mitochondria membranes is close enough to suggest that the two organelles are tethered together by proteins located on the apposing membranes, but they do not fuse and thus the organelles can each maintain their identities.

  • ER–mitochondria contact sites also appear to be stable structures because the two organelles stay tethered to each other even as they move along the cytoskeleton. Contact with the ER is a conserved feature of mitochondrial division sites. This contact is also maintained after fission.

  • Enzymes required for synthesis of a single phospholipid are located on both the ER and the mitochondria. Thus, there are lipid biosynthetic pathways that are thought to occur at ER–mitochondria contact sites.

  • ER contact also directs mitochondrial dynamics in the direction of the bud during inheritance in yeast.

  • Ca2+ is released from the ER to mitochondria at contact sites, and this seems to be important for mitochondrial function, division and regulation of apoptosis.

Abstract

The most well-characterized organelle contact sites are those between the endoplasmic reticulum (ER) and mitochondria. Increased understanding is being gained of how ER–mitochondria contact sites are organized and which factors converge at this interface, some of which may provide a tethering function. The role of the ER–mitochondria junction in coordinating the functions of these two organelles is also becoming clearer, and it has been shown to be involved in the regulation of lipid synthesis, Ca2+ signalling and the control of mitochondrial biogenesis and intracellular trafficking.

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Figure 1: Structure and dynamics of ER–mitochondria contact sites.
Figure 2: ER–mitochondria contact sites mediate lipid biosynthesis.
Figure 3: ER–mitochondria contacts are important for mitochondrial dynamics.
Figure 4: Multiple roles of Ca2+ transfer between the ER and mitochondrial membranes.

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Acknowledgements

We thank J. Shaw and J. Friedman for helpful comments on the manuscript. This work was supported by a grant from the US National Institutes of Health (NIH), RO1GM083977, to G.K.V. and by an NIH predoctoral training grant, GM07135, to A.A.R.

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Rowland, A., Voeltz, G. Endoplasmic reticulum–mitochondria contacts: function of the junction. Nat Rev Mol Cell Biol 13, 607–615 (2012). https://doi.org/10.1038/nrm3440

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