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]
^Levine T (September 2004). "Short-range intracellular trafficking of small molecules across endoplasmic reticulum junctions". Trends in Cell Biology. 14 (9): 483–90. doi:10.1016/j.tcb.2004.07.017. PMID 15350976.
^Prinz, William A.; Choudhary, Vineet; Liu, Li-Ka; Lahiri, Sujoy; Kannan, Muthukumar (2017-03-01). "Phosphatidylserine synthesis at membrane contact sites promotes its transport out of the ER". Journal of Lipid Research. 58 (3): 553–562. doi:10.1194/jlr.M072959. ISSN 0022-2275. PMC 5335585. PMID 28119445.
^Elbaz Y, Schuldiner M (November 2011). "Staying in touch: the molecular era of organelle contact sites". Trends in Biochemical Sciences. 36 (11): 616–23. doi:10.1016/j.tibs.2011.08.004. PMID 21958688.
^Csordás G, Weaver D, Hajnóczky G (July 2018). "Endoplasmic Reticulum-Mitochondrial Contactology: Structure and Signaling Functions". Trends in Cell Biology. 28 (7): 523–540. doi:10.1016/j.tcb.2018.02.009. PMC 6005738. PMID 29588129.
^ abPhillips MJ, Voeltz GK (February 2016). "Structure and function of ER membrane contact sites with other organelles". Nature Reviews. Molecular Cell Biology. 17 (2): 69–82. doi:10.1038/nrm.2015.8. PMC 5117888. PMID 26627931.
^Voeltz GK, Rolls MM, Rapoport TA (October 2002). "Structural organization of the endoplasmic reticulum". EMBO Reports. 3 (10): 944–50. doi:10.1093/embo-reports/kvf202. PMC 1307613. PMID 12370207.
^Helle SC, Kanfer G, Kolar K, Lang A, Michel AH, Kornmann B (November 2013). "Organization and function of membrane contact sites". Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1833 (11): 2526–41. doi:10.1016/j.bbamcr.2013.01.028. PMID 23380708.
^Bohnert M, Schuldiner M (May 2018). "Stepping outside the comfort zone of membrane contact site research". Nature Reviews. Molecular Cell Biology. 19 (8): 483–484. doi:10.1038/s41580-018-0022-1. PMC 6287737. PMID 29765158.
^Copeland DE, Dalton AJ (May 1959). "An association between mitochondria and the endoplasmic reticulum in cells of the pseudobranch gland of a teleost". The Journal of Biophysical and Biochemical Cytology. 5 (3): 393–6. doi:10.1083/jcb.5.3.393. PMC 2224680. PMID 13664679.
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