Lysosomal degradation of cell organelles. III. Uptake and disappearance in Kupffer cells of intravenously injected isotope-labeled mitochondria and microsomes in vivo and in vitro.

14C-leucine and 3H-glycerol-labeled microsomes and mitochondria were intravenously injected into a series of highly inbred rats. The uptake and disappearance of the organelles were followed in a crude liver lysosomal fraction and in serum. Approximately half of the injected dose was recovered in the liver, and only smaller amounts were found in lungs, kidneys, spleen, and heart. The clearance in serum was more rapid for microsomes (t1/2, 5 to 15 minutes) than for mitochondria (t1/2 30 to 60 minutes). Both organelles showed a biphasic type of disappearance curve consistent with the two-phase theory of phagocytosis: attachment and engulfment. The estimated half-life for mitochondria of the liver was in the range of 3 to 4 hours, whereas that of the microsomes was considerably longer, or 8 hours. There was an increase of trichloroacetic acid-soluble material in the crude lysosomal fraction up to 2 hours after injection of glycerol-labeled microsomes, whereas the peak was reached at 60 minutes after 14C-leucine labeling. In vitro hydrolysis rate of hydrolysis. Experiments with Kupffer cells previously labeled with Thorotrast and biochemical assay of hydrolysis indicated that there was a lag phase of approximately 10 to 20 minutes before the phagosomes gained acid hydrolases, presumably by fusion with lysosomes. It is concluded at somewhat different rates. The remnants from lipid degradation, in comparison with protein degradation, seem to remain for a longer period within the lysosomal apparatus. These results are compatible with the concept that lysosomes represent an important, and at the present the only well defined locus for organelle turnover.