Internalization of cytoplasmic protein by lysosomes as the mechanism of resident protein turnover in liver.
Long lived, resident proteins comprise more than 99% of the cytoplasmic protein content in rat liver. In perfusion experiments, their overall rate of degradation can be varied from 4.5-5.0%/h with glucagon or stringent amino acid depletion to 1.5%/h with additions of 4-10 times normal plasma amino acids. The aggregate volume of degradative lysosomal components and their content of degradable protein, estimated in homogenate experiments, were found to relate directly to rates of protein breakdown from maximal down to and including the basal state. The rate constant of autophagic vacuole regression, estimated stereologically after stopping their formation with amino acids, was 0.087/min (t1/2 = 8.0 min), and the turnover of cytoplasmic volume during deprivation, calculated from this constant and increases over basal in either newly induced autophagic vacuoles (AVi) or secondary degradative forms, agreed quantitatively with corresponding rates of protein turnover. The fact that the time courses of intralysosomal proteolysis in liver homogenates were identical, despite large differences in the quantity of internalized protein degraded, suggests that the rate constant of intralysosomal digestion in intact hepatocytes is invariant over the full range of regulation. Our findings thus support the hypothesis that all resident proteins are sequestered and degraded by the lysosomal-vacuolar system.
D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D003593:Cytoplasm / Q000378:metabolism*; D005934:Glucagon / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism*; D008297:Male; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D014617:Vacuoles / Q000378:metabolism; D014633:Valine / Q000378:metabolism
D000596:Amino Acids; D007328:Insulin; D011506:Proteins; D005934:Glucagon; D014633:Valine