Physiology of the lysosome

Excerpt

Initially discovered by Christian de Duve in 1955, lysosomes are now known to contain more than 50 acid hydrolases (phosphatases, nucleases, glycosidases, proteases, peptidases, sulphatases and lipases) that can digest most macromolecules of the cell. The breakdown products, such as amino acids, monosaccharides, oligosaccharides and nucleotides, are transported back to the cytosol by specific transporter proteins in the lysosomal membrane. Functional deficiencies of both hydrolytic and non-hydrolytic polypeptides can result in lysosomal storage diseases, which are characterized by the intralysosomal deposition of macromolecules and a multisystemic phenotype. The detailed structure of the lysosome differs depending on the cell type. Most newly synthesized lysosomal hydrolases enter the lysosomal compartment directly via the biosynthetic route. After modification of one or several of their carbohydrates to mannose-6-phosphate moieties in the Golgi apparatus, the acid hydrolases bind mannose-6-phosphate receptors that deliver them to endosomes. As the vacuolar-type H⁺-ATPase leads to acidification during the maturation of the endosomal compartment, the hydrolases dissociate from their receptors, which are then recycled back to the trans-Golgi network or to the cell surface. The sorting of most lysosomal membrane proteins depends on short sequence motifs within their cytoplasmic tails, which are necessary and sufficient to target them to lysosomes. Lysosomes can be involved in various cellular processes, such as cholesterol homeostasis, autophagy, membrane repair, bone and tissue remodelling, pathogen defence, cell signalling and death. These complex functions highlight the fact that the lysosome is a central organelle which is much more than just the wastebasket of the cell.