Membrane contact site

Membrane contact sites (MCS) are close appositions between two organelles. Ultrastructural studies typically reveal an intermembrane distance in the order of the size of a single protein, as small as 10 nm or wider, with no clear upper limit. These zones of apposition are highly conserved in evolution.^[1] These sites are thought to be important to facilitate signalling, and they promote the passage of small molecules, including ions, lipids^[2] and (discovered later) reactive oxygen species.^[3][4] MCS are important in the function of the endoplasmic reticulum (ER),^[5] since this is the major site of lipid synthesis within cells.^[6] The ER makes close contact with many organelles, including mitochondria, Golgi, endosomes, lysosomes, peroxisomes, chloroplasts and the plasma membrane.^[7] Both mitochondria and sorting endosomes undergo major rearrangements leading to fission where they contact the ER.^[5] Sites of close apposition can also form between most of these organelles most pairwise combinations.^[8] First mentions of these contact sites can be found in papers published in the late 1950s mainly visualized using electron microscopy (EM) techniques. Copeland and Dalton described them as “highly specialized tubular form of endoplasmic reticulum in association with the mitochondria and apparently in turn, with the vascular border of the cell”.^[9]