Principles of lysosomal membrane degradation: Cellular topology and biochemistry of lysosomal lipid degradation.

Abstract

Cellular membranes enter the lysosomal compartment by endocytosis, phagocytosis, or autophagy. Within the lysosomal compartment, membrane components of complex structure are degraded into their building blocks. These are able to leave the lysosome and can then be utilized for the resynthesis of complex molecules or can be further degraded. Constitutive degradation of membranes occurs on the surface of intra-endosomal and intra-lysosomal membrane structures. Many integral membrane proteins are sorted to the inner membranes of endosomes and lysosome after ubiquitinylation. In the lysosome, proteins are degraded by proteolytic enzymes, the cathepsins. Phospholipids originating from lipoproteins or cellular membranes are degraded by phospholipases. Water-soluble glycosidases sequentially cleave off the terminal carbohydrate residues of glycoproteins, glycosaminoglycans, and glycosphingolipids. For glycosphingolipids with short oligosaccharide chains, the additional presence of membrane-active lysosomal lipid-binding proteins is required. The presence of lipid-binding proteins overcomes the phase problem of water soluble enzymes and lipid substrates by transferring the substrate to the degrading enzyme or by solubilizing the internal membranes. The lipid composition of intra-lysosomal vesicles differs from that of the plasma membrane. To allow at least glycosphingolipid degradation by hydrolases and activator proteins, the cholesterol content of these intraorganellar membranes decreases during endocytosis and the concentration of bis(monoacylglycero)phosphate, a stimulator of sphingolipid degradation, increases. A considerable part of our current knowledge about mechanism and biochemistry of lysosomal lipid degradation is derived from a class of human diseases, the sphingolipidoses, which are caused by inherited defects within sphingolipid and glycosphingolipid catabolism.

• Authors: Heike Schulze, Thomas Kolter, Konrad Sandhoff
• Journal: Biochimica et biophysica acta (Biochim Biophys Acta) Vol. 1793 Issue 4 Pg. 674-83 (Apr 2009) ISSN: 0006-3002 [Print] Netherlands
• PMID: 19014978 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Glycosphingolipids

Topics

• Animals
• Biochemistry
• Glycosphingolipids (chemistry, metabolism)
• Humans
• Intracellular Membranes (metabolism)
• Lipid Metabolism
• Lysosomes (metabolism)