Lysosomes and protein degradation.
Evidence from studies on mouse peritoneal macrophages using the inhibitor pepstatin confirms lysosomal involvement in basal protein degradation, and extends its relevance to degradation of long half-life and analogue containing proteins. Studies on the ability of MRC-5 (a limited life-span fibroblast line) cells to selectively degrade analogue-containing proteins are described. These indicate that this capacity is retained even in very old cells; indeed such cells show an increased proportion of rapidly-degradable proteins. Analogue containing proteins bind preferentially to lysosomal membranes, and like liver cytosol proteins of short half-life, are selectively endocytosed and degraded by certain cells in culture. Thus membrane binding allowing selective entry to the lysosomal system may be important in controlling rate of degradation of both intracellular and extracellular protein. A method potentially allowing for determination of the rate of autophagy in cells, is described. This should enable further assessment of the quantitative involvement of lysosomes in protein degradation.
D000818:Animals; D002460:Cell Line; D006207:Half-Life; D006801:Humans; D007700:Kinetics; D008247:Lysosomes / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D010436:Pepstatins / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism*
D010436:Pepstatins; D011506:Proteins