Summary
Amino acids are not only substrates for various metabolic pathways, but can also serve as signaling molecules controlling signal transduction pathways. One of these signaling pathways is mTOR-dependent and is activated by amino acids (leucine in particular) in synergy with insulin. Activation of this pathway inhibits autophagy. Because activation of mTOR-mediated signaling also stimulates protein synthesis, it appears that protein synthesis and autophagic protein degradation are reciprocally controlled by the same signaling pathway. Recent developments indicate that amino acid–stimulated mTOR-dependent signaling is subject to complex regulation. The mechanism by which amino acids stimulate mTORdependent signaling (and other signaling pathways), and its molecular connection with the autophagic machinery, is still unknown.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Reggiori, F. and Klionsky, D. J. (2005) Autophagosomes: biogenesis from scratch? Curr. Opin. Cell Biol. 17, 415–422.
Yorimitsu, T. and Klionsky, D. J. (2005) Autophagy: molecular machinery for self-eating. Cell Death. Differ. 12, 1542–1552.
Hara, T., Nakamura, K., Matsui, M., et al. (2006) Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature 441, 885–889.
Komatsu, M., Waguri ,S., Chiba,T., et al. (2006) Loss of autophagy in the central nervous system causes neurodegeneration in mice. Nature 441, 880–884.
Mortimore, G. E. and Schworer, C. M. (1977) Induction of autophagy by amino-acid deprivation in perfused rat liver. Nature 270, 174–176.
Blommaart, E. F., Luiken, J. J., and Meijer, A. J. (1997) Autophagic proteolysis: control and specificity. Histochem. J. 29, 365–385.
Deter, R. L. and De Duve, C. (1967) Influence of glucagon, an inducer of cellular autophagy, on some physical properties of rat liver lysosomes. J. Cell Biol. 33, 437–449.
van Sluijters, D. A., Dubbelhuis, P. F., Blommaart, E. F., and Meijer, A. J. (2000) Amino-acid-dependent signal transduction. Biochem. J. 351, 545–550.
Pattingre, S., Bauvy, C., and Codogno, P. (2003) Amino acids interfere with the ERK1/2-dependent control of macroautophagy by controlling the activation of Raf-1 in human colon cancer HT-29 cells. J. Biol. Chem. 278, 16667–16674.
Häussinger, D., Reinehr, R., and Schliess, F. (2006) The hepatocyte integrin system and cell volume sensing. Acta Physiol (Oxf) 187, 249–255.
Jacinto, E. and Hall, M. N. (2003) Tor signalling in bugs, brain and brawn. Nat. Rev. Mol. Cell Biol. 4, 117–126.
Proud, C. G. (2006) Regulation of protein synthesis by insulin. Biochem. Soc. Trans. 34, 213–216.
Watson, R. T. and Pessin, J. E. (2006) Bridging the GAP between insulin signaling and GLUT4 translocation. Trends Biochem. Sci. 31, 215–222.
Inoki, K., Corradetti, M. N., and Guan, K. L. (2005) Dysregulation of the TSC-mTOR pathway in human disease. Nat. Genet. 37, 19–24.
Dann, S. G. and Thomas, G. (2006) The amino acid sensitive TOR pathway from yeast to mammals. FEBS Lett. 580, 2821–2829.
Holen, I., Gordon, P. B., and Seglen, P. O. (1993) Inhibition of hepatocytic autophagy by okadaic acid and other protein phosphatase inhibitors. Eur. J. Biochem. 215, 113–122.
Luiken, J. J., Blommaart, E. F., Boon, L., van Woerkom, G. M., and 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, 508–511.
Blommaart, E. F., Luiken, J. J., Blommaart, P. J., van Woerkom, G. M., and Meijer, A. J. (1995) Phosphorylation of ribosomal protein S6 is inhibitory for autophagy in isolated rat hepatocytes. J. Biol. Chem. 270, 2320–2326.
Shintani, T. and Klionsky, D. J. (2004) Autophagy in health and disease: a double-edged sword. Science 306, 990–995.
Noda, T. and Ohsumi, Y. (1998) Tor, a phosphatidylinositol kinase homologue, controls autophagy in yeast. J. Biol. Chem. 273, 3963–3966.
Prick, T., Thumm, M., Kohrer, K., Häussinger, D., and vom Dahl, S. (2006) In yeast, loss of Hog1 leads to osmosensitivity of autophagy. Biochem. J. 394, 153–161.
Kimball, S. R., Siegfried, B. A., and Jefferson, L. S. (2004) Glucagon represses signaling through the mammalian target of rapamycin in rat liver by activating AMP-activated protein kinase. J. Biol. Chem. 279, 54103–54109.
Mothe-Satney, I., Gautier, N., Hinault, C., Lawrence, J. C., Jr., and van Obberghen, E. (2004) In rat hepatocytes glucagon increases mammalian target of rapamycin phosphorylation on serine 2448 but antagonizes the phosphorylation of its downstream targets induced by insulin and amino acids. J. Biol. Chem. 279, 42628–42637.
Blommaart, E. F., Krause, U., Schellens, J. P., Vreeling-Sindelarova, H., and Meijer, A. J. (1997) The phosphatidylinositol 3-kinase inhibitors wortmannin and LY294002 inhibit autophagy in isolated rat hepatocytes. Eur. J. Biochem. 243, 240–246.
Tang, X., Wang, L., Proud, C. G., and Downes, C. P. (2003) Muscarinic receptor-mediated activation of p70 S6 kinase 1 (S6K1) in 1321N1 astrocytoma cells: permissive role of phosphoinositide 3-kinase. Biochem. J. 374, 137–143.
Nobukuni, T., Joaquin, M., Roccio, M., et al. (2005) Amino acids mediate mTOR/raptor signaling through activation of class 3 phosphatidylinositol 3OH-kinase. Proc. Natl. Acad. Sci. USA 102, 14238–14243.
Byfield, M. P., Murray, J. T., and Backer, J. M. (2005) hVps34 is a nutrient-regulated lipid kinase required for activation of p70 S6 kinase. J. Biol. Chem. 280, 33076–33082.
Petiot, A., Ogier-Denis, E., Blommaart, E. F., Meijer, A. J., and Codogno, P. (2000) Distinct classes of phosphatidylinositol 3’-kinases are involved in signaling pathways that control macroautophagy in HT-29 cells. J. Biol. Chem. 275, 992–998.
Arico, S., Petiot, A., Bauvy, C., et al. (2001) The tumor suppressor PTEN positively regulates macroautophagy by inhibiting the phosphatidylinositol 3-kinase/protein kinase B pathway. J. Biol. Chem. 276, 35243–35246.
Seglen, P. O. and Gordon, P. B. (1982) 3-Methyladenine: specific inhibitor of autophagic/lysosomal protein degradation in isolated rat hepatocytes. Proc. Natl. Acad. Sci. USA 79, 1889–1892.
Liang, X. H., Jackson, S., Seaman, M., et al. (1999) Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature 402, 672–676.
Kihara, A., Kabeya, Y., Ohsumi, Y., and Yoshimori, T. (2001) Beclin-phosphatidylinositol 3-kinase complex functions at the trans-Golgi network. EMBO Rep. 2, 330–335.
Furuya, N., Yu, J., Byfield, M., Pattingre, S., and Levine, B. (2005) The Evolutionarily Conserved Domain of Beclin 1 is Required for Vps34 Binding, Autophagy and Tumor Suppressor Function. Autophagy 1, 46–52.
Pattingre, S., Tassa, A., Qu, X., et al. (2005) Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy. Cell 122, 927–939.
Tassa, A., Roux, M. P., Attaix, D., and Bechet, D. M. (2003) Class III phosphoinositide 3-kinase–Beclin1 complex mediates the amino acid-dependent regulation of autophagy in C2C12 myotubes. Biochem. J. 376, 577–586.
Mordier, S., Deval, C., Bechet, D., Tassa, A., and Ferrara, M. (2000) Leucine limitation induces autophagy and activation of lysosome-dependent proteolysis in C2C12 myotubes through a mammalian target of rapamycin-independent signaling pathway. J. Biol. Chem. 275, 29900–29906.
Kanazawa, T., Taneike, I., Akaishi, R., et al. (2004) Amino acids and insulin control autophagic proteolysis through different signaling pathways in relation to mTOR in isolated rat hepatocytes. J. Biol. Chem. 279, 8452–8459.
Schliess, F., Richter, L., vom Dahl, S., and Häussinger, D. (2006) Cell hydration and mTOR-dependent signalling. Acta Physiol (Oxf). 187, 223–229.
Hinault, C., Mothe-Satney, I., Gautier, N., Lawrence, J. C., Jr., and van Obberghen, E. (2004) Amino acids and leucine allow insulin activation of the PKB/mTOR pathway in normal adipocytes treated with wortmannin and in adipocytes from db/db mice. FASEB J. 18, 1894–1896.
Isosaki M. (2004) Inhibition of wortmannin activities by amino compounds. Biochem. Biophys. Res. Commun. 324, 1406–1412.
Kamada, Y., Funakoshi, T., Shintani, T., Nagano, K., Ohsumi, M., and Ohsumi, Y. (2000) Tor-mediated induction of autophagy via an Apg1 protein kinase complex. J. Cell Biol. 150, 1507–1513.
Kabeya, Y., Kamada, Y., Baba, M., Takikawa, H., Sasaki, M., and Ohsumi, Y. (2005) Atg17 functions in cooperation with Atg1 and Atg13 in yeast autophagy. Mol. Biol. Cell 16, 2544–2553.
Dennis, P. B., Jaeschke, A., Saitoh, M., Fowler, B., Kozma, S. C., and Thomas, G. (2001) Mammalian TOR: a homeostatic ATP sensor. Science 294, 1102–1105.
Meijer, A. J. and Dubbelhuis, P. F. (2004) Amino acid signalling and the integration of metabolism. Biochem. Biophys. Res. Commun. 313, 397–403.
Kahn, B. B., Alquier, T., Carling, D., and Hardie, D. G. (2005) AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism. Cell Metab. 1, 15–25.
Corradetti, M. N., Inoki, K., Bardeesy, N., DePinho, R. A., and Guan, K. L. (2004) Regulation of the TSC pathway by LKB1: evidence of a molecular link between tuberous sclerosis complex and Peutz-Jeghers syndrome. Genes Dev. 18, 1533–1538.
Cheng, S. W., Fryer, L. G., Carling, D., and Shepherd, P. R. (2004) Thr2446 is a novel mammalian target of rapamycin (mTOR) phosphorylation site regulated by nutrient status. J. Biol. Chem. 279, 15719–15722.
Wang, Z., Wilson, W. A., Fujino, M. A., and Roach, P. J. (2001) Antagonistic controls of autophagy and glycogen accumulation by Snf1p, the yeast homolog of AMP-activated protein kinase, and the cyclin-dependent kinase Pho85p. Mol. Cell Biol.. 21, 5742–5752.
Samari, H. R. and Seglen, P. O. (1998) Inhibition of hepatocytic autophagy by adenosine, aminoimidazole-4-carboxamide riboside, and N6-mercaptopurine riboside. Evidence for involvement of amp-activated protein kinase. J. Biol. Chem. 273, 23758–23763.
Kundu M. and Thompson C. B. (2005) Macroautophagy versus mitochondrial autophagy: a question of fate? Cell Death. Differ. 12., 1484–1489.
Rodriguez-Enriquez S., Kim I., Currin R. T., and Lemasters J. J. (2006) Tracker dyes to probe mitochondrial autophagy (mitophagy) in rat hepatocytes. Autophagy 2, 39–46.
Tettamanti, G., Malagoli, D., Marchesini, E., Congiu, T., de E. M., and Ottaviani, E. (2006) Oligomycin A induces autophagy in the IPLB-LdFB insect cell line. Cell Tissue Res. 326, 179–186.
Feng, Z., Zhang, H., Levine, A. J., and Jin, S. (2005) The coordinate regulation of the p53 and mTOR pathways in cells. Proc. Natl. Acad. Sci. USA 102, 8204–8209.
Levine, A. J., Feng, Z., Mak, T. W., You, H., and Jin, S. (2006) Coordination and communication between the p53 and IGF-1-AKT-TOR signal transduction pathways. Genes Dev. 20, 267–275.
Wu, H., Yang, J. M., Jin, S., Zhang, H., and Hait, W. N. (2006) Elongation factor-2 kinase regulates autophagy in human glioblastoma cells. Cancer Res. 66, 3015–3023.
Browne, G. J., Finn, S. G., and Proud, C. G. (2004) Stimulation of the AMP-activated protein kinase leads to activation of eukaryotic elongation factor 2 kinase and to its phosphorylation at a novel site, serine 398. J. Biol. Chem. 279, 12220–12231.
Meley, D., Bauvy, C., Houben-Weerts, J. H., et al. (2006) AMP-activated protein kinase and the regulation of autophagic proteolysis. J. Biol. Chem. 281,34870–34879.
Martin, P. M. and Sutherland, A. E. (2001) Exogenous amino acids regulate trophectoderm differentiation in the mouse blastocyst through an mTOR-dependent pathway. Dev. Biol. 240, 182–193.
Beugnet, A., Tee, A. R., Taylor, P. M., and Proud, C. G. (2003) Regulation of targets of mTOR (mammalian target of rapamycin) signalling by intracellular amino acid availability. Biochem. J. 372, 555–566.
Lynch, C. J., Fox, H. L., Vary, T. C., Jefferson, L. S., and Kimbal,l S. R. (2000) Regulation of amino acid-sensitive TOR signaling by leucine analogues in adipocytes. J. Cell Biochem. 77, 234–251.
Shigemitsu, K., Tsujishita, Y., Miyake, H., et al. (1999) Structural requirement of leucine for activation of p70 S6 kinase. FEBS Lett. 447, 303–306.
Smith, E. M., Finn, S. G., Tee, A. R., Browne, G. J., and Proud, C. G. (2005) The tuberous sclerosis protein TSC2 is not required for the regulation of the mammalian target of rapamycin by amino acids and certain cellular stresses. J. Biol. Chem. 280, 18717–18727.
Roccio, M., Bos, J. L., and Zwartkruis, F. J. (2006) Regulation of the small GTPase Rheb by amino acids. Oncogene 25, 657–664.
Tzatsos, A. and Kandror, K. V. (2006) Nutrients suppress phosphatidylinositol 3-kinase/Akt signaling via raptor-dependent mTOR-mediated insulin receptor substrate 1 phosphorylation. Mol. Cell Biol. 26, 63–76.
Long, X., Ortiz-Vega, S., Lin, Y., and Avruch, J. (2005) Rheb binding to mammalian target of rapamycin (mTOR) is regulated by amino acid sufficiency. J. Biol. Chem. 280, 23433–23436.
Lynch, C. J., Halle, B., Fujii, H., et al. (2003) Potential role of leucine metabolism in the leucine-signaling pathway involving mTOR. Am. J. Physiol. Endocrinol. Metab. 285, E854–E863.
Xu, G., Kwon, G., Cruz, W. S., Marshall, C. A., and McDaniel, M. L. (2001) Metabolic regulation by leucine of translation initiation through the mTOR-signaling pathway by pancreatic beta-cells. Diabetes 50, 353–360.
Pfaff, E. and Klingenberg, M. (1968) Adenine nucleotide translocation of mitochondria. 1. Specificity and control. Eur. J. Biochem. 6, 66–79.
Goto, S., Chuman, H., Majima, E., and Terada, H. (2002) How does the mitochondrial ADP/ATP carrier distinguish transportable ATP and ADP from untransportable AMP and GTP?Dynamic modeling of the recognition/translocation process in the major substrate binding region. Biochim. Biophys. Acta 1589, 203–218.
Tsuiki, H., Nitta, M., Furuya, A., et al. (1999) A novel human nucleoside diphosphate (NDP) kinase, Nm23-H6, localizes in mitochondria and affects cytokinesis. J. Cell Biochem. 76, 254–269.
Lipskaya, T. Y. and Voinova, V. V. (2005) Functional coupling between nucleoside diphosphate kinase of the outer mitochondrial compartment and oxidative phosphorylation. Biochemistry (Mosc.) 70, 1354–1362.
Board, M., Humm, S., and Newsholme, E. A. (1990) Maximum activities of key enzymes of glycolysis, glutaminolysis, pentose phosphate pathway and tricarboxylic acid cycle in normal, neoplastic and suppressed cells. Biochem. J. 265, 503–509.
Scherz-Shouval, R., Shvets, E., Fass, E., et al. (2007) Reactive oxygen species are essential for autophagy and specifically regulate the activity of Atg4. EMBO J. 26, 1749–1760.
Djavaheri-Mergny, M., Amelotti, M., Mathieu, J., et al. (2006) NF-KappaB activation represses tumor necrosis factor-alpha-induced autophagy. J. Biol. Chem. 281, 30373–30382.
Martin, F., Pintor, J., Rovira, J. M., Ripoll, C., Miras-Portugal, M. T., and Soria, B. (1998) Intracellular diadenosine polyphosphates: a novel second messenger in stimulus-secretion coupling. FASEB J. 12, 1499–1506.
Desai, B. N., Myers, B. R., and Schreiber, S. L. (2002) FKBP12-rapamycin-associated protein associates with mitochondria and senses osmotic stress via mitochondrial dysfunction. Proc. Natl. Acad. Sci. USA 99, 4319–4324.
Schieke, S. M., Phillips, D., McCoy ,J. P., Jr., et al. (2006) The mammalian target of rapamycin (mTOR) pathway regulates mitochondrial oxygen consumption and oxidative capacity. J. Biol. Chem. 281, 27643–27652.
Weekes, J., Hawley, S. A., Corton, J., Shugar, D., and Hardie, D. G. (1994) Activation of rat liver AMP-activated protein kinase by kinase kinase in a purified, reconstituted system. Effects of AMP and AMP analogues. Eur. J. Biochem. 219,751–757.
Dong, J., Qiu, H., Garcia-Barrio, M., Anderson, J., and Hinnebusch, A. G. (2000) Uncharged tRNA activates GCN2 by displacing the protein kinase moiety from a bipartite tRNA-binding domain. Mol. Cell 6, 269–279.
Natarajan, K., Meyer, M. R., Jackson, B. M., et al. (2001) Transcriptional profiling shows that Gcn4p is a master regulator of gene expression during amino acid starvation in yeast. Mol. Cell Biol. 21, 4347–4368.
Cherkasova, V. A. and Hinnebusch, A. G. (2003) Translational control by TOR and TAP42 through dephosphorylation of eIF2alpha kinase GCN2. Genes Dev. 17, 859–872.
Talloczy, Z., Jiang, W., Virgin, H. W., et al. (2002) Regulation of starvation- and virus-induced autophagy by the eIF2alpha kinase signaling pathway. Proc. Natl. Acad. Sci. USA 99, 190–195.
Fang, Y., Vilella-Bach, M., Bachmann, R., Flanigan, A., and Chen, J. (2001) Phosphatidic acid-mediated mitogenic activation of mTOR signaling. Science 294, 1942–1945.
Hornberger, T. A., Chu, W. K., Mak, Y. W., Hsiung, J. W., Huang, S. A., and Chien, S. (2006) The role of phospholipase D and phosphatidic acid in the mechanical activation of mTOR signaling in skeletal muscle. Proc. Natl. Acad. Sci. USA 103, 4741–4746.
Um, S. H., Frigerio, F., Watanabe, M., et al. (2004) Absence of S6K1 protects against age- and diet-induced obesity while enhancing insulin sensitivity. Nature 431, 200–205.
Khamzina, L., Veilleux, A., Bergeron, S., and Marette, A. (2005) Increased activation of the mammalian target of rapamycin pathway in liver and skeletal muscle of obese rats: possible involvement in obesity-linked insulin resistance. Endocrinology 146, 1473–1481.
Um, S. H., D’Alessio, D., and Thomas, G. (2006) Nutrient overload, insulin resistance, and ribosomal protein S6 kinase 1, S6K1. Cell Metab 3, 393–402.
Wijekoon, E. P., Skinner, C., Brosnan, M. E., and Brosnan, J. T. (2004) Amino acid metabolism in the Zucker diabetic fatty rat: effects of insulin resistance and of type 2 diabetes. Can. J. Physiol Pharmacol. 82, 506–514.
Wang, X., Hu, Z., Hu, J., Du, J., and Mitch, W. E. (2006) Insulin resistance accelerates muscle protein degradation: activation of the ubiquitin-proteasome pathway by defects in muscle cell signaling. Endocrinology 147, 4160–4168.
Klionsky, D. J., Meijer, A. J., Codogno, P., Neufeld, T. P., and Scott, R. C. (2005) Autophagy and p70S6 Kinase. Autophagy 1, 59–61.
Scott, R. C., Schuldiner, O., and Neufeld, T. P. (2004) Role and regulation of starvation-induced autophagy in the Drosophila fat body. Dev. Cell. 7, 167–178.
Ravikumar, B., Vacher, C., Berger, Z., et al. (2004) Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease. Nat. Genet. 36, 585–595.
Yamamoto, A., Cremona, M. L., and Rothman, J. E. (2006) Autophagy-mediated clearance of huntingtin aggregates triggered by the insulin-signaling pathway. J. Cell Biol. 172, 719–731.
Meijer, A. J. and Codogno, P. (2004) Regulation and role of autophagy in mammalian cells. Int. J. Biochem. Cell Biol. 36, 2445–2462.
Scarlatti, F., Bauvy, C., Ventruti, A., et al. (2004) Ceramide-mediated macroautophagy involves inhibition of protein kinase B and up-regulation of beclin 1. J. Biol. Chem. 279, 18384–18391.
Hyde, R., Hajduch, E., Powell, D. J., Taylor, P. M., and Hundal, H. S. (2005) Ceramide down-regulates System A amino acid transport and protein synthesis in rat skeletal muscle cells. FASEB J. 19, 461–463.
Häussinger, D., Schliess, F., Dombrowski, F., and vom Dahl, S. (1999) Involvement of p38MAPK in the regulation of proteolysis by liver cell hydration. Gastroenterology 116, 921–935.
vom Dahl, S., Schliess, F., Reissmann, R., et al. (2003) Involvement of integrins in osmosensing and signaling toward autophagic proteolysis in rat liver. J. Biol. Chem. 278, 27088–27095.
Schliess, F., Reissmann, R., Reinehr, R., vom Dahl, S., and Häussinger, D. (2004) Involvement of integrins and Src in insulin signaling toward autophagic proteolysis in rat liver. J. Biol. Chem. 279, 21294–21301.
Turban, S., Beardmore, V. A., Carr, J. M., et al. (2005) Insulin-stimulated glucose uptake does not require p38 mitogen-activated protein kinase in adipose tissue or skeletal muscle. Diabetes 54, 3161–3168.
Mortimore, G. E., Miotto, G., Venerando, R., and Kadowaki, M. (1996) Autophagy. Subcell. Biochem. 27, 93–135.
Meijer, A. J., Gustafson, L. A., Luiken, J. J., et al. (1993) Cell swelling and the sensitivity of autophagic proteolysis to inhibition by amino acids in isolated rat hepatocytes. Eur. J. Biochem. 215, 449–454.
Codogno, P. and Meijer, A. J. (2005) Autophagy and signaling: their role in cell survival and cell death. Cell Death. Differ. 12, 1509–1518.
Levine, B. and Klionsky, D. J. (2004) Development by self-digestion: molecular mechanisms and biological functions of autophagy. Dev. Cell 6, 463–477.
Kondo, Y., Kanzawa, T., Sawaya, R., and Kondo, S. (2005) The role of autophagy in cancer development and response to therapy. Nat. Rev. Cancer 5, 726–734.
Ng, G. and Huang, J. (2005) The significance of autophagy in cancer. Mol. Carcinog. 43, 183–187.
Hait, W. N., Jin, S., and Yang, J. M. (2006) A matter of life or death (or both): understanding autophagy in cancer. Clin. Cancer Res. 12, 1961–1965.
Botti, J., Djavaheri-Mergny, M., Pilatte, Y., and Codogno, P. (2006) Autophagy signaling and the cogwheels of cancer. Autophagy 2, 67–73.
Cuervo, A. M., Bergamini, E., Brunk, U. T., Droge, W., French, M., and Terman, A. (2005) Autophagy and aging: the importance of maintaining “clean” cells. Autophagy 1, 131–140.
Tatar, M., Bartke, A., and Antebi, A. (2003) The endocrine regulation of aging by insulin-like signals. Science 299, 1346–1351.
Katic, M. and Kahn, C. R. (2005) The role of insulin and IGF-1 signaling in longevity. Cell Mol. Life Sci. 62, 320–343.
Melendez, A., Talloczy, Z., Seaman, M., Eskelinen, E. L., Hall, D. H., and Levine, B. (2003) Autophagy genes are essential for dauer development and life-span extension in C. elegans. Science 301, 1387–1391.
Kurosu, H., Yamamoto, M., Clark, J. D., et al. (2005) Suppression of aging in mice by the hormone Klotho. Science 309, 1829–1833.
Haigis, M. C., Mostoslavsky, R., Haigis, K. M., et al. (2006) SIRT4 inhibits glutamate dehydrogenase and opposes the effects of calorie restriction in pancreatic beta cells. Cell 126, 941–954.
Lowell, B. B. and Shulman, G. I. (2005) Mitochondrial dysfunction and type 2 diabetes. Science 307, 384–387.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2008 Humana Press, a part of Springer Science+Business Media, LLC
About this protocol
Cite this protocol
Meijer, A.J. (2008). Amino Acid Regulation of Autophagosome Formation. In: Deretic, V. (eds) Autophagosome and Phagosome. Methods in Molecular Biology™, vol 445. Humana Press. https://doi.org/10.1007/978-1-59745-157-4_5
Download citation
DOI: https://doi.org/10.1007/978-1-59745-157-4_5
Publisher Name: Humana Press
Print ISBN: 978-1-58829-853-9
Online ISBN: 978-1-59745-157-4
eBook Packages: Springer Protocols