Lysosomal degradation of membrane lipids

Abstract 

The constitutive degradation of membrane components takes place in the acidic compartments of a cell, the endosomes and lysosomes. Sites of lipid degradation are intralysosomal membranes that are formed in endosomes, where the lipid composition is adjusted for degradation. Cholesterol is sorted out of the inner membranes, their content in bis(monoacylglycero)phosphate increases, and, most likely, sphingomyelin is degraded to ceramide. Together with endosomal and lysosomal lipid-binding proteins, the Niemann–Pick disease, type C2-protein, the GM2-activator, and the saposins sap-A, -B, -C, and -D, a suitable membrane lipid composition is required for degradation of complex lipids by hydrolytic enzymes.

Abbreviations: BMP, bis(monoacylglycero)phosphate, ESCRT, endosomal sorting complexes required for transport, FRET, fluorescence or Förster resonance energy transfer, GM1, GM2, GM3, ganglioside-nomenclature according to Svennerholm, compare Fig. 1 for structures, GSL, glycosphingolipid, LLBPs, lysosomal lipid-binding proteins, MVBs, multivesicular bodies, NBD, 4-nitrobenzo-2-oxa-1,3-diazol, NPC1, Niemann–Pick disease, type C1-protein, NPC2, Niemann–Pick disease, type C2-protein, ORP, oxysterol binding protein-related protein, PAF, platelet activating factor, PtdIns, phosphatidylinositol, sap, saposin, SAP, sphingolipid activator protein (GM2-activator, sap-A–sap-D), SCP-2, sterol carrier protein-2, sn1, sn2, stereospecific numbering of glycerolipids according to IUPAC

Keywords: Endosome, GM2-activator, Lysosome, Niemann–Pick disease, type C2-protein, Saposin, Sphingolipid activator protein