The ER must maintain a high Ca 2+ concentration for its signaling and biosynthetic activities, so its Ca 2+ levels are approximately 10,000 times higher than that of the cytoplasm.

Ca 2+ exchange is best understood at ER-plasma membrane contact sites.

Functionally, MCSs are involved in the exchange of Ca 2+, lipids, and proteins.Ĭa 2+ exchange occurs at many types of MCSs, including ER-plasma membrane, ER-mitochondria, and ER-endosome contacts. For some of these MCSs, the protein machinery involved remains mysterious. Organelle-organelle contacts occur between many other organelle pairs as well ( Figure 1). Many of these contacts involve the VAP family of proteins on the ER. The ER interacts with the plasma membrane, endosomes, lysosomes, mitochondria, peroxisomes, and lipid droplets (LDs Figure 1). ER-organelle contact sites are among the best characterized MCSs. Often these tethers are part of large multiprotein complexes. These contact sites are generally thought to form via membrane proteins that act as tethers on the interacting organelles. Organelle interactions via membrane contact sitesĭifferent organelles make close contacts with each other via MCSs. Here, we review several functions of organelle interactions at MCSs, and discuss emerging tools and techniques for studying these processes. Indeed, organelles such as autophagosomes and peroxisomes derive membrane from multiple other organelles, including the ER and mitochondria. Organelle interactions also play important roles during organelle biogenesis and growth. For example, division of both mitochondria and endosomes occurs at sites of close contact with endoplasmic reticulum (ER). In addition to the exchange of materials, MCSs play roles in organelle division. Ions, lipids, and proteins can all be transferred from one organelle to another at MCSs, where different organelles are at close apposition ( Figure 1). An emerging theme in cell biology is that organelle-organelle membrane contact sites (MCSs) are hubs of metabolite exchange and organelle remodeling. Nevertheless, cellular organelles must co-ordinate their activities for the cell to function properly as a biological system. This allows for the spatial and temporal separation of incompatible biochemical processes. A hallmark of eukaryotic cells is their organization into membrane-bound compartments (i.e., endoplasmic reticulum, Golgi, endosome, lysosome, peroxisome, lipid droplet and mitochondria).

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