title: Sphingolipids and lysosomal pathologies.
abstract: Endocytosed (glyco)sphingolipids are degraded, together with other membrane lipids in a stepwise fashion by endolysosomal enzymes with the help of small lipid binding proteins, the sphingolipid activator proteins (SAPs), at the surface of intraluminal lysosomal vesicles. Inherited defects in a sphingolipid-degrading enzyme or SAP cause the accumulation of the corresponding lipid substrates, including cytotoxic lysosphingolipids, such as galactosylsphingosine and glucosylsphingosine, and lead to a sphingolipidosis. Analysis of patients with prosaposin deficiency revealed the accumulation of intra-endolysosmal vesicles and membrane structures (IM). Feeding of prosaposin reverses the storage, suggesting inner membrane structures as platforms of sphingolipid degradation. Water soluble enzymes can hardly attack sphingolipids embedded in the membrane of inner endolysosomal vesicles. The degradation of sphingolipids with few sugar residues therefore requires the help of the SAPs, and is strongly stimulated by anionic membrane lipids. IMs are rich in anionic bis(monoacylglycero)phosphate (BMP). This article is part of a Special Issue entitled New Frontiers in Sphingolipid Biology.
authors.affiliation: LIMES, Membrane Biology & Lipid Biochemistry Unit, c/o Kekulé-Institut für Organische Chemie und Biochemie, Universität Bonn, Gerhard-Domagk-Str. 1, D-53115 Bonn, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Schulze
authors.affiliation: LIMES, Membrane Biology & Lipid Biochemistry Unit, c/o Kekulé-Institut für Organische Chemie und Biochemie, Universität Bonn, Gerhard-Domagk-Str. 1, D-53115 Bonn, Germany. Electronic address: sandhoff@uni-bonn.de.
authors.forename: Konrad
authors.initials: K
authors.lastname: Sandhoff
mesh_terms: D000818:Animals; D006801:Humans; D016464:Lysosomal Storage Diseases / Q000378:metabolism* / Q000473:pathology*; D008247:Lysosomes / Q000378:metabolism* / Q000473:pathology*; D049128:Sphingolipid Activator Proteins / Q000378:metabolism; D013107:Sphingolipids / Q000378:metabolism*
chemical_list: D049128:Sphingolipid Activator Proteins; D013107:Sphingolipids
keywords: Lipid storage; Lysosomal lipids; Membrane degradation; Sphingolipid catabolism