Pathways for the Degradation of Intracellular Proteins Within Lysosomes in Higher Eukaryotes

Publisher Summary Cell proteins are continuously being degraded by both lysosomal and nonlysosomal proteases. Lysosomes that are found in almost all eukaryotic cells participate in intracellular protein degradation by various mechanisms. This chapter reviews recent work on these different lysosomal pathways, focusing largely on the mammalian hepatocyte and on mammalian cultured cells, where most of the work was carried out. Lysosomes contain—enclosed within a membrane—40–60 different acid hydrolytic enzymes, including proteases, nucleases, glycosidases, lipases, phospholipases, phosphatases, and sulfatases. The lysosomal membrane also contains several highly glycosylated proteins of poorly defined functions as well as various transport systems that either allow most of the digestive final products to exit from the lysosomal matrix for further catabolism or for reutilization in the cytosol, or transport substrates into lysosomes to aid in the breakdown processes. Besides non-lysosomal pathways, mammalian cells appear to have multiple lysosomal pathways for the degradation of intracellular proteins. The competitive advantage that a cell derives from having so many pathways is that such a variety allows all kind of proteins (cytosolic, organellar, and secretory) to be degraded in quite controlled but versatile ways, at various speeds, and in response to different stimuli.