Regulation of microautophagy and basal protein turnover in rat liver. Effects of short-term starvation.
Basal rates of long-lived (resident) protein degradation in rat liver, measured during perfusion after amino acid suppression of macroautophagy, were shown to be strongly regulated by caloric deprivation, decreasing 70% over 48 h in animals fed a high protein diet and 50% in normal controls. Intralysosomal pools of degradable protein correlated directly with basal turnover over this range, yielding a slope (0.09 min-1) that was virtually identical with previous estimates of macroautophagic turnover. The specific radioactivity of valine released from lysosomes in previously labeled livers was the same as that in plasma in both basal and deprivation-induced states. Quantitative electron microscopy revealed a significant decrease with starvation in the absolute volume of a class of secondary lysosome (type A) previously associated with basal or microautophagy. By contrast, the volumes of other microautophagic forms, which comprised roughly 10% of the total, did not change. Taking 0.087 min-1 as the turnover constant of degradable intralysosomal protein and assuming that the concentration of sequestered protein was the same in all vacuoles as that in cytoplasm, we obtained close agreement between predicted and observed rates of basal protein turnover over the range of regulation. The results support the view that the lysosomal system is the final step in the basal degradation of long-lived proteins in the hepatocyte and that a specific class of secondary lysosome (type A) plays a direct role in its regulation during caloric starvation.
Mortimore
G E
GE
Department of Physiology, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey 17033.
Lardeux
B R
BR
Adams
C E
CE
D000818:Animals; D003593:Cytoplasm / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism; D008854:Microscopy, Electron; D010587:Phagocytosis; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D011917:Rats, Inbred Lew; D013217:Starvation / Q000378:metabolism*; D013997:Time Factors
D011506:Proteins