Inter-organelle membrane contact sites: implications for lipid metabolism
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Inter-organelle membrane contact sites: implications for lipid metabolism Jean E. Vance Abstract This article supplements a recent Perspective by Scorrano et al. in Nature Communications [10 [ (1)]:1287] in which the properties and functions of inter-organelle membrane contact sites were summarized. It is now clear that interorganelle membrane contact sites are widespread in eukaryotic cells and that diverse pairs of organelles can be linked via unique protein tethers. An appropriate definition of what constitutes an inter-organelle membrane contact site was proposed in the Perspective. In addition, the various experimental approaches that are frequently used to study these organelle associations, as well as the advantages and disadvantages of each of these methods, were considered. The nature of the tethers that link the pairs of organelles at the contact sites was discussed in detail and some biological functions that have been ascribed to specific membrane contact sites were highlighted. Nevertheless, the functions of most types of organelle contact sites remain unclear. In the current article I have considered some of the points raised in the Perspective but have omitted detailed information on the roles of membrane contact sites in biological functions such as apoptosis, autophagy, calcium homeostasis and mitochondrial fusion. Instead, I have provided some background on the initial discovery of mitochondriaendoplasmic reticulum membrane contact sites, and have focussed on the known roles of membrane contact sites in inter-organelle lipid transport. In addition, potential roles for membrane contact sites in human diseases are briefly discussed. Keywords: Membrane contact sites, Phospholipid transport, Cholesterol transport, Mitochondria, Mitochondriaassociated membranes (MAM), Endoplasmic reticulum, Plasma membrane
Discussion Background
The Perspective on membrane contact sites that was recently published in Nature Communications [1] summarizes many of the recent advances in our understanding of inter-organelle membrane contact sites. It is now apparent that membrane contact sites have distinct protein, and probably lipid [2], compositions and are widespread in eukaryotic cells from yeast to plants to mammals [reviewed in [3–5]]. Many types of organelles in eukaryotic cells form heterotypic membrane contact sites that have been described and visualized in cells Correspondence: [email protected] Department of Medicine and Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, AB T6G 2S2, Canada
over several decades. For example, contact sites have been observed that link the endoplasmic reticulum (ER) with other organelles such as mitochondria, Golgi, plasma membranes, endosomes, lipid droplets and peroxisomes. Usually, the inter-organelle association is transient and dynamic but can sometimes be stable. The spacing between the two organelles appears to generally be in the range of 10 to 80 nm. It is likely, however, that a specific distance between the two orga
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