Lipid Transport between the Endoplasmic Reticulum and Mitochondria

Mitochondria are partially autonomous organelles that depend on the import of certain proteins and lipids to maintain cell survival and membrane formation. Although phosphatidylglycerol, cardiolipin, and phosphatidylethanolamine are synthesized by mitochondrial enzymes, phosphatidylcholine, phosphatidylinositol, phosphatidylserine, and sterols need to be imported from other organelles. The origin of most lipids imported into mitochondria is the endoplasmic reticulum, which requires interaction of these two subcellular compartments. Recently, protein complexes that are involved in membrane contact between endoplasmic reticulum and mitochondria were identified, but their role in lipid transport is still unclear. In the present review, we describe components involved in lipid translocation between the endoplasmic reticulum and mitochondria and discuss functional as well as regulatory aspects that are important for lipid homeostasis.Biological membranes are major structural components of all cell types. They protect the cell from external influences, organize the interior in distinct compartments and allow balanced flux of components. Besides their specific proteome, organelles exhibit unique lipid compositions, which influence their shape, physical properties, and function. Major lipid classes found in biological membranes are phospholipids, sterols, and sphingolipids.The major “lipid factory” within the cell is the endoplasmic reticulum (ER). It is able to synthesize the bulk of structural phospholipids, sterols, and storage lipids such as triacylglycerols and steryl esters (van Meer et al. 2008). Furthermore, initial steps of ceramide synthesis occur in the ER providing precursors for the formation of complex sphingolipids in other organelles (Futerman 2006). Besides the export of ceramides, the ER supplies a large portion of lipids to other organelles, which cannot produce their own lipids or have a limited capacity to do so. Organelle interaction and transport of lipids require specific carrier proteins, membrane contact sites, tethering complexes, and/or vesicle flux. These processes are highly important for the maintenance of cell structure and survival but are still a matter of dispute. Most prominent organelle interaction partners are the ER and mitochondria. A subfraction of the ER named mitochondria-associated membrane (MAM) (Vance 1990) was described to be involved in lipid translocation to mitochondria. MAM is part of the ER network, which was shown to be in contact or close proximity to the outer mitochondrial membrane (OMM). Contact sites between MAM and mitochondria were assumed to facilitate exchange of components between the two compartments. Interestingly, MAM harbor a number of lipid synthesizing enzymes (Gaigg et al. 1994). Recently, molecular components governing membrane contact between the two organelles were identified (Dolman et al. 2005; Csordás et al. 2006; de Brito and Scorrano 2008; Kornmann et al. 2009; Friedman et al. 2010; Lavieu et al. 2010), although the specific role of these components in lipid translocation is not yet clear.