Lysosomes and Protein Degradation

Considerable evidence from studies with group-specific proteinase inhibitors, in particular pepstatin, the aspartic proteinase inhibitor, implicates lysosomes in turnover of endogenous cellular proteins. Recent experiments using a new group-specific inhibitor of thiol (cysteine) proteinases, Z-Phe-Ala-diazomethyl ketone, are described. Lysosomal participation is most clearly established for the degradation of long half-life proteins in situations in which turnover is accelerated because of nutritional or hormonal deficiencies. Some evidence indicating their involvement in 'basal' proteolysis is also discussed. Whether lysosomal proteolysis is selective remains to be established, and possible approaches to this question are outlined.