FIGURE 1.

Lipid synthesis and breakdown at MCSs in mammalian cells. (A) Schematic illustration of mammalian MCSs. The contact sites discussed in the text are boxed. (B) Lipid metabolism at the ER-mitochondrion contacts, highlighting the linked synthesis of PC, PE, and PS; the detergent-resistant membrane (DRM) (domain enriched in ceramide, cholesterol, and associated proteins; and the biosynthesis of GPI using ER-derived PI and mitochondrion-derived PE. (C) Lipid metabolism at the ER-PM contacts, showing the Sac1-mediated conversion of phosphatidylinositol 4-phosphate (PI4P) to phosphatidylinositol (4,5)-bisphosphate (PIP2) in trans and in cis, and TMEM24-mediated PI transport. (D) Pex5 and ATGL interaction at peroxisome-LD contacts, and TOMM20 and ACBD2/EI2 interaction at mitochondrion-peroxisome contacts. (E) MIGA2-mediated LD-mitochondrion association to supply TAG from mitochondrially derived citrate. (F) The activation of mTORC1 by cholesterol delivered from the ER to the lysosome surface by OSBP, and the transport of cholesterol out of the lysosome lumen by NPC1. CPT, CDP-choline-1,2-diacylglycerol choline phosphotransferase (CPT); EPT, CDP-ethanolamine:1,2-diacylglycerol ethanolamine phosphotransferase; PSS1/2, phosphatidylserine synthase; PEMT, phosphatidylethanolamine methyltransferase; GPAT1, glycerophosphate acyltransferases; SIG-1R, Sigma 1R; PC, phosphatidylcholine; PE, phosphatidylethanolamine; PS, phosphatidylserine; G3P, glycerol-3-phosphatase; LPA, lysophosphatidic acid; GM1, GM1-ganglioside; GPI, glycosylphosphatidylinositol; TMEM24, transmembrane protein 24; PEX5, peroxisomal biogenesis factor 5; ATGL, triglyceride lipase; TOMM20, Translocase of outer mitochondrial membrane 20; ACBD2/EI2, acyl-coenzyme A-binding domain; ACLY, ATP citrate lyase; FASN, fatty acid synthase; NPC1, Niemann-Pick disease, type C1; OSBP, oxysterol-binding protein 1.)