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Autophagic proteolysis: control and specificity

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Abstract

The rate of proteolysis is an important determinant of the intracellular protein content. Part of the degradation of intracellular proteins occurs in the lysosomes and is mediated by macroautophagy. In liver, macroautophagy is very active and almost completely accounts for starvation-induced proteolysis. Factors inhibiting this process include amino acids, cell swelling and insulin. In the mechanisms controlling macroautophagy, protein phosphorylation plays an important role. Activation of a signal transduction pathway, ultimately leading to phosphorylation of ribosomal protein S6, accompanies inhibition of macroautophagy. Components of this pathway may include a heterotrimeric Gi3-protein, phosphatidylinositol 3- kinase and p70S6 kinase. Recent evidence indicates that lysosomal protein degradation can be selective and occurs via ubiquitin- dependent and -independent pathways.

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References

  • Ahlberg, J., Marzella, L. & Glaumann, H. (1982) Uptake and degradation of proteins by isolated rat liver lysosomes. Suggestion of a microautophagic pathway of proteolysis. Lab. Invest.47, 523-32.

    PubMed  CAS  Google Scholar 

  • Aplin, A., Jasianowski, T., Tuttle, D. L., Lenk, S. E. & Dunn, W. A. (1992) Cytoskeletal elements are required for the formation and maturation of autophagic vacuoles. J. Cell. Physiol.152, 458-66.

    PubMed  CAS  Google Scholar 

  • Attaix, D., Taillandier, D., Temparis, S., Larbaud, D., Aurousseau, E., Combaret, L. & Voisin, L. (1994) Regulation of ATP-ubiquitin-dependent proteolysis in muscle wasting. Reprod. Nutr. Dev.34, 583-97.

    PubMed  CAS  Google Scholar 

  • Auger, K. R., Serunian, L. A., Soltoff, S. P., Libby, P. & Cantley, L. C. (1989) PDGF-dependent tyrosine phosphorylation stimulates production of novel poly-phosphoinositides in intact cells. Cell57, 167-75.

    PubMed  CAS  Google Scholar 

  • Baba, M., Takeshige, K., Baba, N. & Ohsumi, Y. (1994) Ultrastructural analysis of the autophagic process in yeast. Detection of autophagosomes and their characterization. J. Cell Biol.124, 903-13.

    PubMed  CAS  Google Scholar 

  • Bailey, J. L., Wang, X., England, B. K., Price, S. R., Ding, X. & Mitch, W. E. (1996) The acidosis of chronic renal failure activates muscle proteolysis in rats by augmenting transcription of genes encoding proteins of the ATP-dependent ubiquitin-proteasome pathway. J. Clin. Invest.97, 1447-53.

    PubMed  CAS  Google Scholar 

  • Baquet, A., Hue, L., Meijer, A. J., Van Woerkom, G. M. & Plomp, P. J. A. M. (1990) Swelling of hepatocytes stimulates glycogen synthesis. J. Biol. Chem.265, 955-9.

    PubMed  CAS  Google Scholar 

  • Baquet, A., Maisin, L. & Hue, L. (1991a) Swelling of rat hepatocytes activates acetylCoA carboxylase in parallel to glycogen synthase. Biochem. J.278, 887-90.

    PubMed  CAS  Google Scholar 

  • Baquet, A., Meijer, A. J. & Hue, L. (1991b) Hepatocyte swelling increases inositol 1,4,5-trisphosphate, calcium and cyclic AMP concentration but antagonizes phosphorylase activation by Ca2+-dependent hormones. FEBS Lett.278, 103-6.

    PubMed  CAS  Google Scholar 

  • Bergamini, E., Del Roso, A., Gori, Z., Masiello, P., Masini, M. & Pollera, M. (1994) Endocrine and amino acid regulation of liver macroautophagy and proteolytic function. Am. J. Physiol.266, G118-22.

    PubMed  CAS  Google Scholar 

  • Blankson, H., Holen, I. & Seglen, P. O. (1995) Disruption of the cytokeratin cytoskeleton and inhibition of hepatic autophagy by okadaic acid. Exp. Cell Res.218, 522-30.

    PubMed  CAS  Google Scholar 

  • Blommaart, E. F. C. & Meijer, A. J. (1996) Phosphatidylinositol 3-kinase activity is essential for autophagy — a mechanism for 3-methyladenine action. 11th International Conference on Proteolysis and Protein Turnover. Abstract 101. Turku, Finland.

  • Blommaart, P. J. E., Zonneveld, D., Meijer, A. J. & Lamers, W. H. (1993) Effects of intracellular amino acid concentrations, cyclic AMP, and dexamethasone on lysosomal proteolysis in primary cultures of perinatal rat hepatocytes. J. Biol. Chem.268, 1610-17.

    PubMed  CAS  Google Scholar 

  • Blommaart, E. F. C., Luiken, J. J. F. P., Blommaart, P. J. E., Van Woerkom, G. M. & Meijer, A. J. (1995) Phosphorylation of ribosomal protein S6 is inhibitory for autophagy in isolated rat hepatocytes. J. Biol. Chem.270, 2320-6.

    PubMed  CAS  Google Scholar 

  • Blommaart, E. F. C., Krause, U., Schellens, J. P. M., Vreeling-SindelÀrovÀ, H. & Meijer, A. J. (1997) The phosphatidylinositol 3-kinase inhibitors wortmannin and LY294002 inhibit autophagy in isolated rat hepatocytes. Eur. J. Biochem.243, 240-6.

    PubMed  CAS  Google Scholar 

  • Bos, J. L. (1995) A target for phosphoinositide 3-kinase: Akt/PKB. Trends Biochem. Sci.20, 441-2.

    PubMed  CAS  Google Scholar 

  • Brown, W. J., De Wald, D. B., Emr, S. D., Plunter, H. & Balch, W. E. (1995) Role for phosphatidylinositol 3-kinase in the sorting and transport of newly synthesized lysosomal enzymes in mammalian cells. J. Cell Biol.130, 781-96.

    PubMed  CAS  Google Scholar 

  • Busch, G. L., Schreiber, R., Dartsch, P. C., VÖlkl, H., Dahl, S. V., HÄussinger, D. & Lang, F. (1994) Involvement of microtubules in the link between cell volume and pH of acidic cellular compartments in rat and human hepatocytes. Proc. Natl. Acad. Sci. USA91, 9165-9.

    PubMed  CAS  Google Scholar 

  • Canuto, R. A., Tessitore, L., Muzio, G., Autelli, R. & Baccino, F. M. (1993) Tissue protein turnover during liver carcinogenesis. Carcinogenesis14, 2581-7.

    PubMed  CAS  Google Scholar 

  • Cardone, M. & Mostov, K. (1995) Wortmannin inhibits transcytosis of dimeric IgA by the polymeric immunoglobulin receptor. FEBS Lett.376, 74-6.

    PubMed  CAS  Google Scholar 

  • Caro, L. H. P. (1989) Studies on the regulation of autophagic proteolysis in isolated rat hepatocytes. PhD thesis, University of Amsterdam.

  • Caro, L. H. P., Plomp, P. J. A. M., Leverve, X. M. & Meijer, A. J. (1989) A combination of intracellular leucine with either glutamate or aspartate inhibits autophagic proteolysis in isolated rat hepatocytes. Eur. J. Biochem.181, 717-20.

    PubMed  CAS  Google Scholar 

  • Cheatham, B., Vlahos, C. J., Cheatham, L., Wang, L., Blenis, J. & Kahn, C. R. (1994) Phosphatidylinositol 3-kinase activation is required for insulin stimulation of pp70 S6 kinase, DNA synthesis, and glucose transporter translocation. Mol. Cell. Biol.14, 4902-11.

    PubMed  CAS  Google Scholar 

  • Chiang, H. L. & Schekman, R. (1991) Regulated import and degradation of a cytosolic protein in the yeast vacuole. Nature350, 313-18.

    PubMed  CAS  Google Scholar 

  • Chiang, H. L., Schekman, R. & Hamamoto, S. (1996) Selective uptake of cytosolic, peroxisomal, and plasma membrane proteins into the yeast lysosome for degradation. J. Biol. Chem.271, 9934-41.

    PubMed  CAS  Google Scholar 

  • Chou, M. M. & Blenis, J. (1995) The 70 kDa S6 kinase: regulation of a kinase with multiple roles in mitogenic signalling. Curr. Biol.7, 806-14.

    CAS  Google Scholar 

  • Chua, B. H. L. (1994) Specificity of leucine effect on protein degradation in perfused rat heart. J. Mol. Cell. Cardiol.26, 743-51.

    PubMed  CAS  Google Scholar 

  • Chung, J., Grammer, T. C., Lemon, K. P., Kazlauskas, A. & Blenis, J. (1994) PDGF-and insulin-dependent pp70S6k activation mediated by phosphatidylinositol-3-OH kinase. Nature370, 71-5.

    PubMed  CAS  Google Scholar 

  • Clague, M. J., Thorpe, C. & Jones, A. T. (1995) Phosphatidylinositol 3-kinase regulation of fluid phase endocytosis. FEBS Lett.367, 272-4.

    PubMed  CAS  Google Scholar 

  • Clarke, J. F., Young, P. W., Yonezawa, K., Kasuga, M. & Holman, G. D. (1994) Inhibition of the translocation of GLUT1 and GLUT4 in 3T3-L1 cells by the phosphatidylinositol 3-kinase inhibitor, wortmannin. Biochem. J.300, 631-5.

    PubMed  CAS  Google Scholar 

  • Collot, M., Louvard, D. & Singer, S. J. (1984) Lysosomes are associated with microtubules and not with intermediate filaments in fibroblasts. Proc. Natl. Acad. Sci. USA81, 788-92.

    PubMed  CAS  Google Scholar 

  • Cuervo, A. M. & Dice, J. F. (1996) A receptor for the selective uptake and degradation of proteins by lysosomes. Science273, 501-3.

    PubMed  CAS  Google Scholar 

  • Cuervo, A. M., Knecht, E., Terlecki, S. R. & Dice, J. F. (1995) Activation of a selective pathway of lysosomal proteolysis in rat liver by prolonged starvation. Am. J. Physiol.269, C1200-8.

    PubMed  CAS  Google Scholar 

  • Dahn, M. S., Hsu, C. J., Lange, M. P., Kimball, S. R. & Jefferson, L. S. (1993) Factors affecting secretory protein production in primary cultures of rat hepatocytes. Proc. Soc. Exp. Biol. Med.203, 38-44.

    PubMed  CAS  Google Scholar 

  • Davidson, H. W. (1995) Wortmannin causes mistargeting of procathepsin D. The involvement of a phosphatidylinositol 3-kinase in vesicular transport to lysosomes. J. Cell. Biol.130, 797-805.

    PubMed  CAS  Google Scholar 

  • De Waal, E. J., Vreeling-SindelÁrovÁ, H., Schellens, J. P. M., Houtkoper, J. M. & James, J. (1986) Quantitative changes in the lysosomal vacuolar system of rat hepatocytes during short-term starvation. A morphometric analysis with special reference to macro-and micro-autophagy. Cell Tissue Res.234, 641-8.

    Google Scholar 

  • Dice, J. F. (1990) Peptide sequences that target cytosolic proteins for lysosomal proteolysis. Trends Biochem. Sci.15, 305-9.

    PubMed  CAS  Google Scholar 

  • Dilling, M. B., Dias, P., Shapiro, D. N., Germain, G. S., Johnson, R. K. & Houghton, P. J. (1994) Rapamycin selectively inhibits the growth of childhood rhabdomyosarcoma cells through inhibition of signaling via the type I insulin-like growth factor receptor. Cancer Res.54, 903-7.

    PubMed  CAS  Google Scholar 

  • Doherty, F. J., Osborne, N. U., Wassell, J. A., Heggie, P. E., Laszlo, L. & Mayer, R. J. (1989) Ubiquitin-protein conjugates accumulate in the lysosomal system of fibroblasts treated with cysteine proteinase inhibitors. Biochem. J.263, 47-55.

    PubMed  CAS  Google Scholar 

  • Dunn, W. A. (1990a) Studies on the mechanisms of autophagy: formation of the autophagic vacuole. J. Cell Biol.110, 1923-33.

    PubMed  Google Scholar 

  • Dunn, W. A. (1990b) Studies on the mechanisms of autophagy: maturation of the autophagic vacuole. J. Cell Biol.110, 1935-45.

    PubMed  CAS  Google Scholar 

  • Dunn, W. A. (1994) Autophagy and related mechanisms of lysosome-mediated protein degradation. Trends Cell Biol.4, 139-43.

    PubMed  CAS  Google Scholar 

  • Evans, J. L., Honer, C. M., Womelsdorf, B. E., Kaplan, E. L. & Bell, P. A. (1995) The effects of wortmannin, a potent inhibitor of phosphatidylinositol 3-kinase, on insulin stimulated glucose transport, GLUT4 translocation, antilipolysis, and DNA synthesis. Cell Signalling7, 365-76.

    PubMed  CAS  Google Scholar 

  • Falconer, I. R. & Yeung, D. S. (1992) Cytoskeletal changes in hepatocytes induced by microcystis toxins and their relation to hyperphosphorylation of cell proteins. Chem. Biol. Interactions81, 181-96.

    CAS  Google Scholar 

  • Fengsrud, M., Roos, N., Berg, T., Liou, W. L., Slot, J. W. & Seglen, P. O. (1995) Ultrastructural and immunocytochemical characterization of autophagic vacuoles in isolated hepatocytes: effects of vinblastine and asparagine on vacuole distributions. Exp. Cell Res.221, 504-19.

    PubMed  CAS  Google Scholar 

  • Finn, P. J., Plank, L. D., Clark, M. A., Connolly, A. B. & Hill, G. L. (1996) Progressive cellular dehydration and proteolysis in critically ill patients. Lancet347, 654-6.

    PubMed  CAS  Google Scholar 

  • Fosse, H., Berg, T. O., Oreilly, D. S. J. & Seglen, P. O. (1995) Vanadate inhibition of hepatocytic autophagy — calcium-modulated and osmolality-modulated antagonism by asparagine. Eur. J. Biochem.230, 17-24.

    PubMed  CAS  Google Scholar 

  • Ghidoni, R., Houri, J. J., Giuliani, A., Ogier-Denis, E., Parolari, E., Botti, S., Bauvy, C. & Codogno, P. (1996) The metabolism of sphingo(glyco)lipids is correlated with the differentiation-dependent autophagic pathway in HT-29 cells. Eur. J. Biochem.237, 454-9.

    PubMed  CAS  Google Scholar 

  • Gordon, P. B. & Seglen, P. O. (1988) Prelysosomal convergence of autophagic and endocytic pathways. Biochem. Biophys. Res. Commun.151, 40-7.

    Article  PubMed  CAS  Google Scholar 

  • Gordon, P. B., Hoyvik, H. & Seglen, P. O. (1992) Prelysosomal and lysosomal connections between autophagy and endocytosis. Biochem. J.283, 361-9.

    PubMed  Google Scholar 

  • Gordon, P. B., Holen, I., Fosse, M., Rotnes, J. S. & Seglen, P. O. (1993) Dependence of hepatocytic autophagy on intracellularly sequestered calcium. J. Biol. Chem.268, 26107-12.

    PubMed  CAS  Google Scholar 

  • Gordon, P. B., Holen, I. & Seglen, P. O. (1995) Protection by naringin and some other flavonoids of hepatocytic autophagy and endocytosis against inhibition by okadaic acid. J. Biol. Chem.270, 5830-8.

    PubMed  CAS  Google Scholar 

  • Gropper, R., Brandt, R. A., Elias, S., Bearer, C. F., Mayer, A., Schwartz, A. L. & Ciechanover, A. (1991) The ubiquitin-activating enzyme, E1, is required for stress-induced lysosomal degradation of cellular proteins. J. Biol. Chem.266, 3602-10.

    PubMed  CAS  Google Scholar 

  • Hall, M. N. (1995) The TOR signalling pathway and growth control in yeast. Biochem. Soc. Trans.24, 234-9.

    Google Scholar 

  • Hallbrucker, C., Vom Dahl, S., Lang, F. & HÄussinger, D. (1991a) Control of hepatic proteolysis by amino acids. The role of cell volume. Eur. J. Biochem.197, 717-24.

    PubMed  CAS  Google Scholar 

  • Hallbrucker, C., Vom Dahl, S., Lang, F., Gerok, W. & HÄussinger, D. (1991b) Inhibition of hepatic proteolysis by insulin. Role of hormone-induced alterations of the cellular K+ balance. Eur. J. Biochem.199, 467-74.

    PubMed  CAS  Google Scholar 

  • HÄussinger, D. (1996) The role of cellular hydration in the regulation of cell function. Biochem. J.313, 697-710.

    PubMed  Google Scholar 

  • HÄussinger, D. & Lang, F. (1991) Cell volume in the regulation of hepatic function: a mechanism for metabolic control. Biochim. Biophys. Acta1071, 331-50.

    PubMed  Google Scholar 

  • HÄussinger, D., Hallbrucker, C., Vom Dahl, S., Lang, F. & Gerok, W. (1990) Cell swelling inhibits proteolysis in perfused rat liver. Biochem. J.272, 239-42.

    PubMed  Google Scholar 

  • HÄussinger, D., Roth, E., Lang, F. & Gerok, W. (1993) Cellular hydration state, an important determinant of protein catabolism in health and disease. Lancet341, 1330-2.

    PubMed  Google Scholar 

  • Heikoop, J. C., Van Den Berg, M., Strijland, A., Weijers, P. J., Just, W. W., Meijer, A. J. & Tager, J. M. (1992) Turnover of peroxisomal vesicles by autophagic proteolysis in cultured fibroblasts from Zellweger patients. Eur. J. Cell Biol.57, 165-71.

    PubMed  CAS  Google Scholar 

  • Hershko, A. & Ciechanover, A. (1992) The ubiquitin system for protein degradation. Ann. Rev. Biochem.61, 761-807.

    PubMed  CAS  Google Scholar 

  • Hilt, W. & Wolf, D. H. (1996) Proteasomes: destruction as a programme. Trends Biochem. Sci.21, 96-102.

    PubMed  CAS  Google Scholar 

  • Hoffmann, E. K. & Simonsen, L. O. (1989) Membrane mechanisms in volume and pH regulation in vertebrate cells. Physiol. Rev.69, 315-82.

    PubMed  CAS  Google Scholar 

  • Holen, I., Gordon, P. B. & Seglen, P. O. (1992) Protein kinase-dependent effects of okadaic acid on hepatocytic autophagy and cytoskeletal integrity. Biochem. J.284, 633-6.

    PubMed  CAS  Google Scholar 

  • Holen, I., Gordon, P. B. & Seglen, P. O. (1993) Inhibition of hepatic autophagy by okadaic acid and other protein phosphatase inhibitors. Eur. J. Biochem.215, 113-22.

    PubMed  CAS  Google Scholar 

  • Holen, I., StrØmhaug, P. E., Gordon, P. B., Fengsrud, M., Berg, T. O. & Seglen, P. O. (1995) Inhibition of autophagy and multiple steps in asialoglycoprotein endocytosis by inhibitors of tyrosine protein kinases (tyrphostins). J. Biol. Chem.270, 12823-31.

    PubMed  CAS  Google Scholar 

  • Houri, J. J., Ogier-Denis, E., Trugnan, G. & Codogno, P. (1993) Autophagic degradation of N-linked glycoproteins is downregulated in differentiated human colon adenocarcinoma cells. Biochem. Biophys. Res. Commun.197, 805-11.

    PubMed  CAS  Google Scholar 

  • Houri, J. J., Ogier-Denis, E., De Stefanis, D., Bauvy, C., Baccino, F., Isidoro, C. & Codogno, P. (1995) Differentiation-dependent autophagy controls the fate of newly synthesized N-linked glycoproteins in the colon adenocarcinoma HT-29 cell line. Biochem. J.309, 521-7.

    PubMed  Google Scholar 

  • HØyvik, H., Gordon, P. B. & Seglen, P. O. (1986) Use of a hydrolysable probe, [14C]lactose, to distinguish between pre-lysosomal and lysosomal steps in the autophagic pathway. Exp. Cell Res.166, 1-14.

    PubMed  Google Scholar 

  • HØyvik, H., Gordon, P. B., Berg, T. O., StrØmhaug, P. E. & Seglen, P. O. (1991) Inhibition of autophagic-lysosomal delivery and autophagic lactolysis by asparagine. J. Cell Biol.113, 1305-12.

    PubMed  Google Scholar 

  • Ichimura, T., Ohsumi, T., Shindo, Y., Ohwada, T., Yagame, H., Momose, Y., Omata, S. & Sugano, H. (1992) Isolation and some properties of a 34-kDa-membrane protein that may be responsible for ribosome binding in rat liver rough microsomes. FEBS Lett.296, 7-10.

    PubMed  CAS  Google Scholar 

  • Jefferies, H. B. J., Reinhard, C., Kozma, S. C. & Thomas, G. (1994) Rapamycin selectively represses translation of the ‘polypyrimidine tract’ mRNA family. Proc. Natl. Acad. Sci. USA91, 4441-5.

    PubMed  CAS  Google Scholar 

  • Jennissen, H. P. (1995) Ubiquitin and the enigma of intracellular protein degradation. Eur. J. Biochem.231, 1-30.

    PubMed  CAS  Google Scholar 

  • Jones, A. T. & Clague, M. J. (1995) Phosphatidylinositol 3-kinase activity is required for early endosome fusion. Biochem. J.311, 31-4.

    PubMed  CAS  Google Scholar 

  • Kadowaki, M., Venerando, R., Miotto, G. & Mortimore, G. E. (1994) De novo autophagic vacuole formation in hepatocytes permeabilized by Staphylococcus aureus ·-toxin. Inhibition by nonhydrolysable GTP analogs. J. Biol. Chem.269, 3703-10.

    PubMed  CAS  Google Scholar 

  • Kalies, K.-U., GÖrlich, D. & Rapoport, T. A. (1994) Binding of ribosomes to the rough endoplasmic reticulum mediated by the Sec61p-complex. J. Cell Biol.126, 925-34.

    PubMed  CAS  Google Scholar 

  • Kelly, K. L. & Ruderman, N. B. (1993) Insulin-stimulated phosphatidyl-inositol 3-kinase. Association with a 185-kDa tyrosine phosphorylated protein (IRS-1) and localization in a low density membrane vesicle. J. Biol. Chem.268, 4391-8.

    PubMed  CAS  Google Scholar 

  • Kisen, G. Ø., Tessitore, L., Costelli, P., Gordon, P. B., Schwarze, P. E., Baccino, F. M. & Seglen, P. O. (1993) Reduced autophagic activity in primary rat hepatocellular carcinoma and ascites hepatoma cells. Carcinogenesis14, 2501-5.

    PubMed  CAS  Google Scholar 

  • Kominami, E., Hashida, S., Khairallah, E. A. & Katunuma, N. (1983) Sequestration of cytoplasmic enzymes in autophagic vacuole-lysosomal system induced by injection with leupeptin. J. Biol. Chem.258, 6093-100.

    PubMed  CAS  Google Scholar 

  • Kopitz, J., Kisen, G. Ø., Gordon, P. B., Bohley, P. & Seglen, P. O. (1990) Nonselective autophagy of cytosolic enzymes by isolated rat hepatocytes. J. Cell Biol.111, 941-53.

    PubMed  CAS  Google Scholar 

  • KovÁcs, A. L., Grinde, B. & Seglen, P. O. (1981) Inhibition of autophagic vacuole formation and protein degradation by amino acids in isolated rat hepatocytes. Exp. Cell Res.133, 431-6.

    PubMed  Google Scholar 

  • KovÁcs, A. L., Reith, A. & Seglen, P. O. (1982) Accumulation of autophagosomes after inhibition of hepatocyte protein degradation by vinblastin, leupeptin or a lysosomotropic amine. Exp. Cell Res.137, 191-201.

    PubMed  Google Scholar 

  • Kozma, S. C. & Thomas, G. (1992) Serine/threonine kinases in the propagation of the early mitogenic response. Rev. Physiol. Biochem. Pharmacol.119, 123-55.

    PubMed  CAS  Google Scholar 

  • Krause, U., Rider, M. H. & Hue, L. (1996) Protein kinase signaling pathway triggered by cell swelling is involved in the activation of glycogen synthase and acetyl-CoA carboxylase in isolated rat hepatocytes. J. Biol. Chem.271, 16668-73.

    PubMed  CAS  Google Scholar 

  • Lang, F., Stehle, T. & HÄussinger, D. (1989) Water, K+, H+, lactate and glucose fluxes during cell volume regulation in perfused rat liver. Pflügers Arch.413, 209-16.

    PubMed  CAS  Google Scholar 

  • Lardeux, B. R. & Mortimore, G. E. (1987) Amino acid and hormonal control of macromolecular turnover in perfused rat liver. Evidence for selective autophagy. J. Biol. Chem.262, 14514-19.

    PubMed  CAS  Google Scholar 

  • Laszlo, L., Doherty, F. J., Osborne, N. U. & Mayer, R. J. (1990) Ubiquitinated protein conjugates are specifically enriched in the lysosomal system of fibroblasts. FEBS Lett.261, 365-8.

    PubMed  CAS  Google Scholar 

  • Lauring, B., Sakai, H., Kreibich, G. & Wiedmann, M. (1995) Nascent polypeptide-associated complex protein prevents mistargeting of nascent chains to the endoplasmic reticulum. Proc. Natl. Acad. Sci. USA92, 5411-15.

    PubMed  CAS  Google Scholar 

  • Lawrence, B. P. & Brown, W. J. (1992) Autophagic vacuoles rapidly fuse with pre-existing lysosomes in cultured hepatocytes. J. Cell Sci.102, 515-26.

    PubMed  Google Scholar 

  • Lenk, S. E., Dunn, W. A., Trausch, J. S., Ciechanover, A. & Schwartz, A. L. (1992) Ubiquitin-activating enzyme, E1, is associated with maturation of autophagic vacuoles. J. Cell Biol.118, 301-8.

    PubMed  CAS  Google Scholar 

  • Leverve, X. M., Caro, L. H. P., Plomp, P. J. A. M. & Meijer, A. J. (1987) Control of proteolysis in perifused hepatocytes. FEBS Lett.219, 455-8.

    PubMed  CAS  Google Scholar 

  • Li, G. P., D'Souza-Schorey, C., Barbieri, M. A., Roberts, R. L., Klippel, A., Williams, L. T. & Stahl, P. D. (1995) Evidence for phosphatidylinositol 3-kinase as a regulator of endocytosis via activation of Rab5. Proc. Natl. Acad. Sci. USA92, 10207-11.

    PubMed  CAS  Google Scholar 

  • Llovera, M., Garcia-Martinez, C., Agell, N., Lopezsoriano, F. J. & Argiles, J. M. (1995) Muscle wasting associated with cancer cachexia is linked to an important activation of the ATP-dependent ubiquitin-mediated proteolysis. Int. J. Cancer61, 138-41.

    PubMed  CAS  Google Scholar 

  • Low, S. Y., Taylor, P. M. & Rennie, M. J. (1996) Responses of glutamine transport in cultured rat skeletal muscle to osmotically induced changes in cell volume. J. Physiol. London492, 877-85.

    PubMed  CAS  Google Scholar 

  • Luiken, J. J. F. P. (1996) Specificity and regulation of autophagic proteolysis in rat hepatocytes. PhD thesis, University of Amsterdam.

  • Luiken, J. J. F. P., Van Den Berg, M., Heikoop, J. C. & Meijer, A. J. (1992) Autophagic degradation of peroxisomes in isolated hepatocytes. FEBS Lett.304, 93-7.

    PubMed  CAS  Google Scholar 

  • Luiken, J. J. F. P., Blommaart, E. F. C., Boon, L., Van Woerkom, G. M. & Meijer, A. J. (1994) Cell swelling and the control of autophagic proteolysis in hepatocytes: involvement of phosphorylation of ribosomal protein S6? Biochem. Soc. Trans.22, 508-11.

    PubMed  CAS  Google Scholar 

  • Luiken, J. J. F. P., Aerts, J. M. F. G. & Meijer, A. J. (1996) The role of the intralysosomal pH in the control of autophagic proteolytic flux in rat hepatocytes. Eur. J. Biochem.235, 564-73.

    Article  PubMed  CAS  Google Scholar 

  • Masaki, R., Yamamoto, A. & Tashiro, Y. (1987) Cytochrome P-450 and NADPH-cytochrome P-450 reductase are degraded in the autolysosomes in rat liver. J. Cell Biol.104, 1207-15.

    PubMed  CAS  Google Scholar 

  • Mayer, R. J. & Doherty, F. (1986) Intracellular protein catabolism: state of the art. FEBS Lett.198, 181-93.

    PubMed  CAS  Google Scholar 

  • Mayer, R. J., Arnold, J., Laszlo, L., Landon, M. & Lowe, L. (1991) Ubiquitin in health and disease. Biochim. Biophys. Acta1089, 141-57.

    PubMed  CAS  Google Scholar 

  • Medina, R., Wing, S. S. & Goldberg, A. L. (1995) Increase in levels of polyubiquitin and proteasome mRNA in skeletal muscle during starvation and denervation atrophy. Biochem. J.307, 631-7.

    PubMed  CAS  Google Scholar 

  • Meijer, A. J. (1995) Inhibition of autophagic proteolysis by cell swelling in hepatocytes. Biochem. J.312, 987-8.

    PubMed  CAS  Google Scholar 

  • Meijer, A. J., Lamers, W. H. & Chamuleau, R. A. F. M. (1990) Nitrogen metabolism and ornithine cycle function. Physiol. Rev.70, 701-48.

    PubMed  CAS  Google Scholar 

  • Meijer, A. J., Baquet, A., Gustafson, L., Van Woerkom, G. M. & Hue, L. (1992) Mechanism of activation of liver glycogen synthase by swelling. J. Biol. Chem.267, 5823-8.

    PubMed  CAS  Google Scholar 

  • Meijer, A. J., Gustafson, L. A., Luiken, J. J. F. P., Blommaart, P. J. E., Caro, L. H. P., Van Woerkom, G. M., Spronk, C. & Boon, L. (1993) Cell swelling and the sensitivity of autophagic proteolysis to inhibition by amino acids in isolated rat hepatocytes. Eur. J. Biochem.215, 449-54.

    PubMed  CAS  Google Scholar 

  • Mellgren, R. L. (1987) Calcium-dependent proteases: an enzyme system active at cellular membranes? FASEB J.1, 110-5.

    PubMed  CAS  Google Scholar 

  • Miotto, G., Venerando, R., Khurana, K. K., Siliprandi, N. & Mortimore, G. E. (1992) Control of hepatic proteolysis by leucine and isovaleryl-L-carnitine through a common locus. Evidence for a possible mechanism of recognition at the plasma membrane. J. Biol. Chem.267, 22066-72.

    PubMed  CAS  Google Scholar 

  • Miotto, G., Venerando, R., Marin, O., Siliprandi, N. & Mortimore, G. E. (1994) Inhibition of macroautophagy and proteolysis in the isolated rat hepatocyte by a non-transportable derivative of the multiple antigen peptide leu8-lys4-lys2-lys-· ala. J. Biol. Chem.269, 25348-53.

    PubMed  CAS  Google Scholar 

  • Monfar, M., Lemon, K. P., Grammer, T. C., Cheatham, L., Chung, J., Vlahos, C. J. & Blenis, J. (1995) Activation of pp70/85 S6 kinases in interleukin-2-responsive lymphoid cells is mediated by phosphatidylinositol 3-kinase and inhibited by cyclic AMP. Mol. Cell. Biol.15, 326-37.

    PubMed  CAS  Google Scholar 

  • Morley, S. J. & Traugh, J. A. (1993) Stimulation of translation in 3T3-L1 cells in response to insulin and phorbol ester is directly correlated with increased phosphate labelling of initiation factor (eiF-)4F and ribosomal protein S6. Biochimie75, 985-9.

    PubMed  CAS  Google Scholar 

  • Mortimore, G. E., Hutson, N. J. & Surmacz, C. A. (1983) Quantitative correlation between proteolysis and macro-and microautophagy in mouse hepatocytes during starvation and refeeding. Proc. Natl. Acad. Sci. USA80, 2179-83.

    PubMed  CAS  Google Scholar 

  • Mortimore, G. E., PÖsÖ, A. R., Kadowaki, M. & Wert, J. J. Jr. (1987) Multiphasic control of hepatic protein degradation by regulatory amino acids. General features and hormonal regulation. J. Biol. Chem.262, 16322-7.

    PubMed  CAS  Google Scholar 

  • Mortimore, G. E., Lardeux, B. R. & Adams, C. E. (1988a) Regulation of microautophagy and basal protein turnover in rat liver. Effects of short-term starvation. J. Biol. Chem.263, 2506-12.

    PubMed  CAS  Google Scholar 

  • Mortimore, G. E., Wert, J. J. & Adams, C. E. (1988b) Modulation of the amino acid control of hepatic protein degradation by caloric deprivation. J. Biol. Chem.263, 19545-51.

    PubMed  CAS  Google Scholar 

  • Mortimore, G. E., PÖsÖ, A. R. & Lardeux, B. R. (1989) Mechanism and regulation of protein degradation in liver. Diabetes/Metabolism Rev.5, 49-70.

    Article  CAS  Google Scholar 

  • Mortimore, G. E., Khurana, K. K. & Miotto, G. (1991) Amino acid control of proteolysis in perfused livers of synchronously fed rats. J. Biol. Chem.266, 1021-8.

    PubMed  CAS  Google Scholar 

  • Mortimore, G. E., Wert, J. J., Miotto, G., Venerando, R. & Kadowaki, M. (1994) Leucine-specific binding of photoreactive leu7-MAP to a high molecular weight protein on the plasma membrane of the isolated rat hepatocyte. Biochem. Biophys. Res. Commun.203, 200-8.

    PubMed  CAS  Google Scholar 

  • Muller, S. & Schwartz, L. M. (1995) Ubiquitin in homeostasis, development and disease. BioEssays17, 677-84.

    PubMed  CAS  Google Scholar 

  • Nakanishi, H. N., Brewer, K. A. & Exton, J. H. (1993) Activation of the zeta isozyme of protein kinase C by phosphatidylinositol 3,4,5-trisphosphate. J. Biol. Chem.268, 13-16.

    PubMed  CAS  Google Scholar 

  • NavÉ, B. T., Siddle, K. & Shepherd, P. R. (1996) Phorbol esters stimulate phosphatidylinositol 3,4,5-trisphosphate production in 3T3-L1 adipocytes — implications for stimulation of glucose transport. Biochem. J.318, 203-5.

    PubMed  Google Scholar 

  • Neu, J., Shenoy, V. & Chakrabarti, R. (1996) Glutamine nutrition and metabolism: where do we go from here? FASEB J.10, 829-37.

    PubMed  CAS  Google Scholar 

  • Nishizuka, Y. (1992) Intracellular signaling by hydrolysis of phospholipids and activation of protein kinase C. Science258, 607-14.

    PubMed  CAS  Google Scholar 

  • Ogier-Denis, E., Couvineau, A., Maoret, J. J., Houri, J. J., Bauvy, C., De Stefanis, D., Isidoro, C., Laburthe, M. & Codogno, P. (1995) A heteromeric Gi3-protein controls autophagic sequestration in the human cancer cell line HT-29. J. Biol. Chem.270, 13-16.

    PubMed  CAS  Google Scholar 

  • Ogier-Denis, E., Houri, J. J., Bauvy, C. & Codogno, P. (1996) Guanine nucleotide exchange on heterotrimeric Gi3 protein controls autophagic sequestration in HT-29 cells. J. Biol. Chem.271, 28593-600.

    PubMed  CAS  Google Scholar 

  • Olkkonen, V. M., Dupree, P., Killisch, I., Lutcke, A., Zerial, M. & Simons, K. (1993) Molecular cloning and subcellular localization of three GTP-binding proteins of the Rab subfamily. J. Cell Sci.106, 1249-61.

    PubMed  CAS  Google Scholar 

  • Palen, E. & Traugh, J. A. (1987) Phosphorylation of ribosomal protein S6 by cAMP dependent protein kinase and mitogen-stimulated S6 kinase differentially alters translation of globin mRNA. J. Biol. Chem.262, 3518-23.

    PubMed  CAS  Google Scholar 

  • Parrilla, R., Goodman, M. N. & Toews, C. J. (1974) Effect of glucagon:insulin ratios on hepatic metabolism. Diabetes23, 725-31.

    PubMed  CAS  Google Scholar 

  • Partin, J., Schubert, W. K. & Partin, J. S. (1971) Mitochondrial ultrastructure in Reye's syndrome (encephalopathy and fatty degeneration of the viscera). N. Engl. J. Med.285, 1339-43.

    Article  PubMed  CAS  Google Scholar 

  • Paskin, N. & Mayer, R. J. (1977) The role of enzyme degradation in enzyme turnover during tissue differentiation. Biochim. Biophys. Acta474, 1-10.

    PubMed  CAS  Google Scholar 

  • Pfeifer, U. (1987) Functional morphology of the lysosomal apparatus. In Lysosomes, their role in protein breakdown (edited by Glaumann, H. & Ballard, F. J.), pp. 4-59. London: Academic Press.

    Google Scholar 

  • Pfeifer, U., Werde, E. & Bergeest, H. (1978) Inhibition by insulin of the formation of autophagic vacuoles. A morphometric approach to the kinetics of intracellular degradation by autophagy. J. Cell. Biol.78, 152-67.

    PubMed  CAS  Google Scholar 

  • Plomp, P. J. A. M., Wolvetang, E. J., Groen, A. K., Meijer, A. J., Gordon, P. B. & Seglen, P. O. (1988) Energy dependence of autophagic protein degradation in isolated rat hepatocytes. Eur. J. Biochem.164, 197-203.

    Google Scholar 

  • Plomp, P. J. A. M., Gordon, P. B., Meijer, A. J., HØyvik, H. & Seglen, P. O. (1989) Energy dependence of different steps in the autophagic-lysosomal pathway. J. Biol. Chem.254, 6699-704.

    Google Scholar 

  • PÖsÖ, A. R. & Mortimore, G. E. (1984) Requirement for alanine in the amino acid control of deprivation induced protein degradation in liver. Proc. Natl. Acad. Sci. USA81, 4270-4.

    PubMed  Google Scholar 

  • Proud, C. G. (1996) p70 S6 kinase: an enigma with variations. Trends Biochem Sci21, 181-5.

    PubMed  CAS  Google Scholar 

  • Quon, M. J., Chen, H., Ing, B. L., Liu, M. L., Zarnowski M. J., Yonezawa, K., Kasuga, M., Cushman, S. W. & Taylor, S. I. (1995) Roles of 1-phosphatidylinositol 3-kinase and ras in regulating translocation of GLUT4 in transfected rat adipose cells. Mol. Cell. Biol.15, 5403-11.

    PubMed  CAS  Google Scholar 

  • Rabkin, R., Tsao, T., Shi, J. D. & Mortimore, G. E. (1991) Amino acids regulate kidney cell protein breakdown. J. Lab. Clin. Med.117, 505-13.

    PubMed  CAS  Google Scholar 

  • Rennie, M. J., Babij, P., Taylor, P. M., Hundal, H. S., Mclennan, P., Watt, P. W., Jepson, M. M. & Millward, R. J. (1986) Characteristics of a glutamine carrier in skeletal muscle have important consequences for nitrogen loss in injury, infection and chronic disease. Lancet2, 1008-12.

    PubMed  CAS  Google Scholar 

  • RÉz, G., Kiss, A., Buseck, M. J. & KovÁcs, J. (1976) Attachment of ribosomes to endoplasmic membranes in mouse pancreas. Degranulation in vivo caused by the inducers of autophagocytosis neutral red, vinblastine, puromycin, and cadmium ions, and prevention by cycloheximide. Chem. Biol. Interactions13, 77-87.

    Google Scholar 

  • Saido, T. C., Sorimachi, H. & Suzuki, K. (1994) Calpain: new perspectives in molecular diversity and physiological-pathological involvement. FASEB J.8, 814-22.

    PubMed  CAS  Google Scholar 

  • Sakai, M., Araki, N. & Ogawa, K. (1989) Lysosomal movements during heterophagy and autophagy: with special reference to nematolysosome and wrapping lysosome. J. Electron Microsc. Tech.12, 101-31.

    PubMed  CAS  Google Scholar 

  • Savitz, A. J. & Meyer, D. I. (1993) 180-kD ribosome receptor is essential for both ribosome binding and protein translocation. J. Cell Biol.120, 853-63.

    PubMed  CAS  Google Scholar 

  • Schellens, J. P. M. & Meijer, A. J. (1991) Energy depletion and autophagy. Cytochemical and biochemical studies in isolated rat hepatocytes. Histochem. J.23, 460-6.

    PubMed  CAS  Google Scholar 

  • Schork, S. M., Thumm, M. & Wolf, D. H. (1995) Catabolite inactivation of fructose-1,6-bisphosphatase of Saccharomyces cerevisiae. Degradation occurs via the ubiquitin pathway. J. Biol. Chem.270, 26446-50.

    PubMed  CAS  Google Scholar 

  • Schreiber, R. & HÄussinger, D. (1995) Characterization of the swelling-induced alkalinization of endocytotic vesicles in fluorescein isothiocyanate-dextran-loaded rat hepatocytes. Biochem. J.309, 19-24.

    PubMed  CAS  Google Scholar 

  • Schreiber, R., Zhang, F. & HÄussinger, D. (1996) Regulation of vesicular pH in liver macrophages and parenchymal cells by ammonia and anisotonicity as assessed by fluorescein isothiocyanate-dextran fluorescence. Biochem. J.315, 385-92.

    PubMed  CAS  Google Scholar 

  • Schu, P. V., Takegawa, K., Fry, M. J., Stack, J. H., Waterfield, M. D. & Emr, S. D. (1993) Phosphatidylinositol 3-kinase encoded by yeast VPS34 gene essential for protein sorting. Science260, 88-91.

    PubMed  CAS  Google Scholar 

  • Schwartz, A. L., Ciechanover, A., Brandt, R. A. & Geuze, H. J. (1988) Immunoelectron microscopic localization of ubiquitin in hepatoma cells. EMBO J.7, 2961-6.

    PubMed  CAS  Google Scholar 

  • Schwartz, A. L., Brandt, R. A., Geuze, H. & Ciechanover, A. (1992) Stress-induced alterations in autophagic pathway: relationship to ubiquitin system. Am. J. Physiol.262, C1031-8.

    PubMed  CAS  Google Scholar 

  • Schwarze, P. E. & Seglen, P. O. (1985) Reduced autophagic activity, improved protein balance and enhanced in vitro survival of hepatocytes isolated from carcinogen-treated rats. Exp. Cell Res.157, 15-28.

    PubMed  CAS  Google Scholar 

  • Schworer, C. M. & Mortimore, G. E. (1979) Glucagon induced autophagy and proteolysis in rat liver: mediation by selective deprivation of intracellular amino acids. Proc. Natl. Acad. Sci. USA76, 3169-73.

    PubMed  CAS  Google Scholar 

  • Seglen, P. O. (1987) Regulation of autophagic protein degradation in isolated liver cells. In Lysosomes, their Role in Protein Breakdown (edited by Glaumann, H. & Ballard, F. J.), pp. 371-414. London: Academic Press.

    Google Scholar 

  • Seglen, P. O. & Bohley, P. (1992) Autophagy and other vacuolar protein degradation mechanisms. Experientia48, 158-72.

    PubMed  CAS  Google Scholar 

  • Seglen, P. O. & Gordon, P. B. (1982) 3-Methyladenine: specific inhibitor of autophagic/lysosomal protein degradation in isolated rat hepatocytes. Proc. Natl. Acad. Sci. USA79, 1889-92.

    PubMed  CAS  Google Scholar 

  • Seglen, P. O. & Gordon, P. B. (1984) Amino acid control of autophagic sequestration and protein degradation. J. Cell Biol.99, 435-44.

    PubMed  CAS  Google Scholar 

  • Seglen, P. O., Gordon, P. B. & Poli, A. (1980) Amino acid inhibition of the autophagic/lysosomal pathway of protein degradation in isolated rat hepatocytes. Biochim. Biophys. Acta630, 103-18.

    PubMed  CAS  Google Scholar 

  • Shepherd, P. R., Reaves, B. J. & Davidson, H. W. (1996) Phosphoinositide 3-kinases and membrane traffic. Trends Cell Biol.6, 92-7.

    PubMed  CAS  Google Scholar 

  • Stack, J. H. & Emr, S. D. (1994) VPS34p required for yeast vacuolar protein sorting is a multiple specificity kinase that exhibits both protein kinase and phosphatidylinositol-specific PI 3-kinase activities. J. Biol. Chem.269, 31552-62.

    PubMed  CAS  Google Scholar 

  • Stehle, P., Mertens, N., Puchstein, C. H., Zander, J., Albers, S., Lawin, P. & FÜrst, P. (1989) Effect of parenteral glutamine peptide supplements on muscle glutamine loss and nitrogen balance after major surgery. Lancet1, 231-3.

    PubMed  CAS  Google Scholar 

  • Stoll, B., Gerok, W., Lang, F. & HÄussinger, D. (1992) Liver cell volume and protein synthesis. Biochem. J.287, 217-22.

    PubMed  CAS  Google Scholar 

  • StrØmhaug, P. E. & Seglen, P. O. (1993) Evidence for acidity of prelysosomal autophagic/endocytic vacuoles (amphisomes). Biochem. J.291, 115-21.

    PubMed  Google Scholar 

  • Sturgill, T. W. & Wu, J. (1991) Recent progress in characterization of protein kinase cascades for phosphorylation of ribosomal protein S6. Biochim. Biophys. Acta1092, 350-7.

    PubMed  CAS  Google Scholar 

  • Swanson, J. A., Locke, A., Ansel, P. & Hollenbeck, P. J. (1992) Radial movement of lysosomes along microtubules in permeabilized macrophages. J. Cell Sci.103, 201-9.

    PubMed  CAS  Google Scholar 

  • Tanaka, K. & Ichihara, A. (1983) Different effects of amino acid deprivation on synthesis of intra-and extracellular proteins in rat hepatocytes in primary culture. J. Biochem.94, 1339-48.

    PubMed  CAS  Google Scholar 

  • Terada, N., Patel, H. R., Takase, K., Kohno, K., Nairn, A. C. & Gelfand, E. W. (1994) Rapamycin selectively inhibits translation of mRNAs encoding elongation factors and ribosomal proteins. Proc. Natl. Acad. Sci. USA91, 11477-81.

    PubMed  CAS  Google Scholar 

  • Terlecki, S. R., Chiang, H. L., Olson, T. S. & Dice, J. F. (1992) Protein and peptide binding and stimulation of in vitro lysosomal proteolysis by the 73-kDa heat shock cognate protein. J. Biol. Chem.267, 9202-9.

    Google Scholar 

  • Terlecki, S. R. (1994) Hsp70s and lysosomal proteolysis. Experientia50, 1021-5.

    Google Scholar 

  • Terlecki, S. R. & Dice, J. F. (1993) Polypeptide import and degradation by isolated lysosomes. J. Biol. Chem.268, 23490-5.

    Google Scholar 

  • Tessitore, L., Bonelli, G., Cecchini, G., Autelli, R., Amenta, J. S. & Baccino, F. M. (1988) Regulation of protein turnover versus growth state. Studies of the mechanism of initiation of acidic vacuolar proteolysis in cells of stationary ascites hepatoma. Biochem. J.251, 483-90.

    PubMed  CAS  Google Scholar 

  • Thumm, M., Egner, R., Koch, B., Schlumpberger, M., Straub, M., Veenhuis, M. & Wolf, D. H. (1994) Isolation of autophagocytosis mutants of Saccharomyces cerevisiae. FEBS Lett.349, 275-80.

    PubMed  CAS  Google Scholar 

  • Tiao, G., Fagan, J., Roegner, V., Lieberman, M., Wang, J. J., Fischer, J. E. & Hasselgren, P. O. (1996) Energy-ubiquitin-dependent muscle proteolysis during sepsis in rats is regulated by glucocorticoids. J. Clin. Invest.97, 339-48.

    PubMed  CAS  Google Scholar 

  • Titorenko, V. I., Keizer, I., Harder, W. & Veenhuis, M. (1995) Isolation and characterization of mutants impaired in the selective degradation of peroxisomes in the yeast Hansenula polymorpha. J. Bacteriol.177, 357-63.

    PubMed  CAS  Google Scholar 

  • Tooze, J., Hollinshead, M., Ludwig, T., Howell, K., Hoflack, B. & Kern, H. (1990) In exocrine pancreas, the basolateral endocytic pathway converges with the autophagic pathway immediately after the early endosome. J. Cell Biol.111, 329-45.

    PubMed  CAS  Google Scholar 

  • Tsukada, M. & Ohsumi, Y. (1993) Isolation and characterization of autophagy-defective mutants of Saccharomyces cerevisiae. FEBS Lett.333, 169-74.

    PubMed  CAS  Google Scholar 

  • Tuttle, D. L. & Dunn, W. A. (1995) Divergent modes of autophagy in the methylotrophic yeast Pichia pastoris. J. Cell Sci.108, 25-35.

    PubMed  CAS  Google Scholar 

  • Tuttle, D. L., Lewin, A. S. & Dunn, W. A. (1993) Selective autophagy of peroxisomes in methylotrophic yeasts. Eur. J. Cell Biol.60, 283-90.

    PubMed  CAS  Google Scholar 

  • Veenhuis, M., Douma, A., Harder, W. & Osumi, M. (1983) Degradation and turnover of peroxisomes in the yeast Hansenula polymorpha induced by selective inactivation of peroxisomal enzymes. Arch. Microbiol.134, 193-203.

    PubMed  CAS  Google Scholar 

  • Venerando, R., Miotto, G., Kadowaki, M., Siliprandi, N. & Mortimore, G. E. (1994) Multiphasic control of proteolysis by leucine and alanine in the isolated rat hepatocyte. Am. J. Physiol.266, C455-61.

    PubMed  CAS  Google Scholar 

  • VÖlkl, H., Friedrich, F., HÄussinger, D. & Lang, F. (1993) Effect of cell volume on acridine orange fluorescence in hepatocytes. Biochem. J.295, 11-14.

    PubMed  Google Scholar 

  • Vom Dahl, S. & HÄussinger, D. (1995) Cell hydration and proteolysis control in liver. Biochem. J.312, 988-9.

    PubMed  CAS  Google Scholar 

  • Vom Dahl, S., Stoll, B., Gerok, W. & HÄussinger, D. (1995) Inhibition of proteolysis by cell swelling in the liver requires intact microtubular structures. Biochem. J.308, 529-36.

    PubMed  Google Scholar 

  • Ways, D. K., Cook, P. P., Webster, C. & Parker, P. J. (1992) Effect of phorbol esters on protein kinase C-zeta. J. Biol. Chem.267, 4799-805.

    PubMed  CAS  Google Scholar 

  • Wetsel, W. C., Khan, W. A., Merchenthaler, I., Rivera, H., Halpern, A. E., Phung, H. M., Negrovilar, A. & Hannun, Y. A. (1992) Tissue and cellular distribution of the extended family of protein kinase C isoenzymes. J. Cell Biol.117, 121-33.

    PubMed  CAS  Google Scholar 

  • Wettenhall, R. E. H., Cohen, P., Caudwell, B. & Holland, R. (1982) Differential phosphorylation of ribosomal protein S6 in isolated rat hepatocytes after incubation with insulin and glucagon. FEBS Lett.148, 207-13.

    PubMed  CAS  Google Scholar 

  • Wilson, M., Burt, A. R., Milligan, G. & Anderson, N. G. (1996) Wortmannin-sensitive activation of p70s6k by endogenous and heterologously expressed Gi-coupled receptors. J. Biol. Chem.271, 8537-40.

    PubMed  CAS  Google Scholar 

  • Wing, S. S. & Goldberg, A. L. (1993) Glucocorticoids activate the ATP-ubiquitin-dependent proteolytic system in skeletal muscle during fasting. Am. J. Physiol.264, E668-76.

    PubMed  CAS  Google Scholar 

  • Wing, S. S., Chiang, H. L. Goldberg, A. L. & Dice, J. F. (1991) Proteins containing peptide sequences related to Lys-Phe-Glu-Arg-Gln are selectively depleted in liver and heart, but not skeletal muscle, of fasted rats. Biochem. J.275, 165-9.

    PubMed  CAS  Google Scholar 

  • Woodfin, B. M. & Davis, L. E. (1986) Liver autophagy in the influenza B virus model of Reye's syndrome in mice. J. Cell. Biochem.31, 271-5.

    PubMed  CAS  Google Scholar 

  • Yamamoto, A., Masaki, R. & Tashiro, Y. (1990a) Characterization of the isolation membranes and the limiting membranes of autophagosomes in rat hepatocytes by lectin cytochemistry. J. Histochem. Cytochem.38, 573-80.

    PubMed  CAS  Google Scholar 

  • Yamamoto, A., Masaki, R., Fukui, Y. & Tashiro, Y. (1990b) Absence of cytochrome P-450 and presence of autolysosomal membrane antigens on the isolation membranes and autophagosomal membranes in rat hepatocytes. J. Histochem. Cytochem.38, 1571-81.

    PubMed  CAS  Google Scholar 

  • Yamamoto-Honda, R., Tobe, K., Kaburagi, Y., Ueki, K., Asai, S., Yachi, M., Shirouzu, M., Yodoi, J., Akanuma, Y., Yokoyama, S., Yazaki, Y. & Kadowaki, T. (1995) Upstream mechanisms of glycogen synthase activation by insulin and insulin-like growth factor-I. Glycogen synthase activation is antagonized by wortmannin or LY294002 but not by rapamycin or by inhibiting p21ras. J. Biol. Chem.270, 2729-34.

    PubMed  CAS  Google Scholar 

  • Yano, T., Tokui, T., Nishi, Y., Nishizawa, K., Shibata, M., Kikuchi, K., Tsuiki, S., Yamauchi, T. & Inagaki, M. (1991) Phosphorylation of keratin intermediate filaments by protein kinase C, by calmodulin-dependent protein kinase and by cAMP-dependent protein kinase. Eur. J. Biochem.197, 281-90.

    PubMed  CAS  Google Scholar 

  • Yi, J., Zhang, H. X., Zhang, L. & Tang, X. M. (1993) Lysosomes in the regulation of hormone secretion in the pituitary-adrenal gland axis. Acta Biol. Exp. Sinica26, 221-31.

    PubMed  CAS  Google Scholar 

  • Yokota, S. (1993) Formation of autophagosomes during degradation of excess peroxisomes induced by administration of dioctyl phthalate. Eur. J. Cell Biol.61, 67-80.

    PubMed  CAS  Google Scholar 

  • Yokota, S., Himeno, M. & Kato, K. (1994) Degradation of excess peroxisomes by cellular autophagy: immunocytochemical and biochemical analysis. Acta Histochem. Cytochem.27, 573-9.

    Google Scholar 

  • Yokota, S., Himeno, M. & Kato, K. (1995) Formation of autophagosomes during degradation of excess peroxisomes induced by di-(2-ethylhexyl)-phthalate treatment. III. Fusion of early autophagosomes with lysosomal compartments. Eur. J. Cell Biol.66, 15-24.

    PubMed  CAS  Google Scholar 

  • Yokota, S., Himeno, M., Roth, J., Brada, D. & Kato, K. (1993) Formation of autophagosomes during degradation of excess peroxisomes induced by di-(2-ethylhexyl)phthalate treatment. 2. Immunocytochemical analysis of early and late autophagosomes. Eur. J. Cell Biol.62, 372-83.

    PubMed  CAS  Google Scholar 

  • Yucel, T., Ahlberg, J. & Glaumann, H. (1989) Overall proteolysis in perfused and subfractionated chemically induced malignant hepatoma of rat: effects of amino acids. Exp. Mol. Pathol.50, 38-49.

    PubMed  CAS  Google Scholar 

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  1. Department of Biochemistry, University of Amsterdam, Academic Medical Centre, Meibergdreef 15, 1105 AZ, Amsterdam, The Netherlands

    E. F. C. Blommaart, J. J. F. P. Luiken & A. J. Meijer

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Blommaart, E.F.C., Luiken, J.J.F.P. & Meijer, A.J. Autophagic proteolysis: control and specificity. J Mol Hist 29, 365–385 (1997). https://doi.org/10.1023/A:1026486801018

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