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Chemical modulators of autophagy as biological probes and potential therapeutics

Nature Chemical Biology volume 7, pages 9–17 (2011)Cite this article

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Abstract

Autophagy is an evolutionarily conserved mechanism for protein degradation that is critical for the maintenance of homeostasis in man. Autophagy has unexpected pleiotropic functions that favor survival of the cell, including nutrient supply under starvation, cleaning of the cellular interior, defense against infection and antigen presentation. Moreover, defective autophagy is associated with a diverse range of disease states, including neurodegeneration, cancer and Crohn's disease. Here we discuss the roles of mammalian autophagy in health and disease and highlight recent advances in pharmacological manipulation of autophagic pathways as a therapeutic strategy for a variety of pathological conditions.

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Figure 1: Schematic of autophagy.
Figure 2: Schematic representation of the mTOR signaling pathway.
Figure 3: mTOR-independent autophagy induction pathways.

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References

  1. Yoshimori, T. Autophagy: a regulated bulk degradation process inside cells. Biochem. Biophys. Res. Commun. 313, 453–458 (2004).

    Article  CAS  PubMed  Google Scholar 

  2. Yu, L. et al. Termination of autophagy and reformation of lysosomes regulated by mTOR. Nature 465, 942–946 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Nakatogawa, H., Suzuki, K., Kamada, Y. & Ohsumi, Y. Dynamics and diversity in autophagy mechanisms: lessons from yeast. Nat. Rev. Mol. Cell Biol. 10, 458–467 (2009).

    Article  CAS  PubMed  Google Scholar 

  4. Hosokawa, N. et al. Nutrient-dependent mTORC1 association with the ULK1-Atg13–FIP200 complex required for autophagy. Mol. Biol. Cell 20, 1981–1991 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Kroemer, G., Marino, G. & Levine, B. Autophagy and the integrated stress response. Mol. Cell 40, 280–293 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Simonsen, A. & Tooze, S.A. Coordination of membrane events during autophagy by multiple class III PI3-kinase complexes. J. Cell Biol. 186, 773–782 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Noda, T., Matsunaga, K., Taguchi-Atarashi, N. & Yoshimori, T. Regulation of membrane biogenesis in autophagy via PI3P dynamics. Semin. Cell Dev. Biol. 21, 671–676 (2010).

    CAS  Google Scholar 

  8. Fujita, N. et al. The Atg16L complex specifies the site of LC3 lipidation for membrane biogenesis in autophagy. Mol. Biol. Cell 19, 2092–2100 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Fujita, N. et al. An Atg4B mutant hampers the lipidation of LC3 paralogues and causes defects in autophagosome closure. Mol. Biol. Cell 19, 4651–4659 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Sou, Y.S. et al. The Atg8 conjugation system is indispensable for proper development of autophagic isolation membranes in mice. Mol. Biol. Cell 19, 4762–4775 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Webber, J.L. & Tooze, S.A. New insights into the function of Atg9. FEBS Lett. 584, 1319–1326 (2010).

    Article  CAS  PubMed  Google Scholar 

  12. Matsunaga, K. et al. Autophagy requires endoplasmic reticulum targeting of the PI3-kinase complex via Atg14L. J. Cell Biol. 190, 511–521 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Yousefi, S. et al. Calpain-mediated cleavage of Atg5 switches autophagy to apoptosis. Nat. Cell Biol. 8, 1124–1132 (2006).

    Article  CAS  PubMed  Google Scholar 

  14. Zhao, Z. et al. Autophagosome-independent essential function for the autophagy protein Atg5 in cellular immunity to intracellular pathogens. Cell Host Microbe 4, 458–469 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Saitoh, T. et al. Atg9a controls dsDNA-driven dynamic translocation of STING and the innate immune response. Proc. Natl. Acad. Sci. USA 106, 20842–20846 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Radoshevich, L. et al. ATG12 conjugation to ATG3 regulates mitochondrial homeostasis and cell death. Cell 142, 590–600 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Tooze, S.A. & Yoshimori, T. The origin of the autophagosomal membrane. Nat. Cell Biol. 12, 831–835 (2010).

    Article  CAS  PubMed  Google Scholar 

  18. Hailey, D.W. et al. Mitochondria supply membranes for autophagosome biogenesis during starvation. Cell 141, 656–667 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Ravikumar, B., Moreau, K., Jahreiss, L., Puri, C. & Rubinsztein, D.C. Plasma membrane contributes to the formation of pre-autophagosomal structures. Nat. Cell Biol. 12, 747–757 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Tsukamoto, S., Kuma, A. & Mizushima, N. The role of autophagy during the oocyte-to-embryo transition. Autophagy 4, 1076–1078 (2008).

    Article  PubMed  Google Scholar 

  21. Tsukamoto, S. et al. Autophagy is essential for preimplantation development of mouse embryos. Science 321, 117–120 (2008).

    Article  CAS  PubMed  Google Scholar 

  22. Eisenberg, T. et al. Induction of autophagy by spermidine promotes longevity. Nat. Cell Biol. 11, 1305–1314 (2009).

    Article  CAS  PubMed  Google Scholar 

  23. Kuma, A. et al. The role of autophagy during the early neonatal starvation period. Nature 432, 1032–1036 (2004).

    Article  CAS  PubMed  Google Scholar 

  24. Heilbronn, L.K. & Ravussin, E. Calorie restriction and aging: review of the literature and implications for studies in humans. Am. J. Clin. Nutr. 78, 361–369 (2003).

    Article  CAS  PubMed  Google Scholar 

  25. Vellai, T. Autophagy genes and ageing. Cell Death Differ. 16, 94–102 (2009).

    Article  CAS  PubMed  Google Scholar 

  26. Simonsen, A. et al. Promoting basal levels of autophagy in the nervous system enhances longevity and oxidant resistance in adult Drosophila. Autophagy 4, 176–184 (2008).

    Article  CAS  PubMed  Google Scholar 

  27. Zheng, S. et al. Deletion of the huntingtin polyglutamine stretch enhances neuronal autophagy and longevity in mice. PLoS Genet. 6, e1000838 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Harrison, D.E. et al. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature 460, 392–395 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Morselli, E. et al. The life span-prolonging effect of sirtuin-1 is mediated by autophagy. Autophagy 6, 186–188 (2010).

    Article  PubMed  Google Scholar 

  30. Armour, S.M. et al. Inhibition of mammalian S6 kinase by resveratrol suppresses autophagy. Aging (Albany NY) 1, 515–528 (2009).

    Article  CAS  Google Scholar 

  31. Opipari, A.W. Jr. et al. Resveratrol-induced autophagocytosis in ovarian cancer cells. Cancer Res. 64, 696–703 (2004).

    Article  CAS  PubMed  Google Scholar 

  32. Tavernarakis, N., Pasparaki, A., Tasdemir, E., Maiuri, M.C. & Kroemer, G. The effects of p53 on whole organism longevity are mediated by autophagy. Autophagy 4, 870–873 (2008).

    Article  CAS  PubMed  Google Scholar 

  33. Ravikumar, B. et al. Regulation of Mammalian autophagy in physiology and pathophysiology. Physiol. Rev. 90, 1383–1435 (2010).

    Article  CAS  PubMed  Google Scholar 

  34. Thurston, T.L., Ryzhakov, G., Bloor, S., von Muhlinen, N. & Randow, F. The TBK1 adaptor and autophagy receptor NDP52 restricts the proliferation of ubiquitin-coated bacteria. Nat. Immunol. 10, 1215–1221 (2009).

    Article  CAS  PubMed  Google Scholar 

  35. Parkes, M. et al. Sequence variants in the autophagy gene IRGM and multiple other replicating loci contribute to Crohn's disease susceptibility. Nat. Genet. 39, 830–832 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Rioux, J.D. et al. Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis. Nat. Genet. 39, 596–604 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Saitoh, T. et al. Loss of the autophagy protein Atg16L1 enhances endotoxin-induced IL-1beta production. Nature 456, 264–268 (2008).

    CAS  PubMed  Google Scholar 

  38. Stappenbeck, T.S. et al. Crohn disease: A current perspective on genetics, autophagy and immunity. Autophagy 7 1–20 (2011).

    Article  CAS  Google Scholar 

  39. Mizushima, N. & Hara, T. Intracellular quality control by autophagy: how does autophagy prevent neurodegeneration? Autophagy 2, 302–304 (2006).

    Article  CAS  PubMed  Google Scholar 

  40. García-Arencibia, M., Hochfeld, W.E., Toh, P.P. & Rubinsztein, D.C. Autophagy, a guardian against neurodegeneration. Semin. Cell Dev. Biol. 21, 691–698 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. Ravikumar, B. et al. Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease. Nat. Genet. 36, 585–595 (2004).

    Article  CAS  PubMed  Google Scholar 

  42. Zhang, L. et al. Small molecule regulators of autophagy identified by an image-based high-throughput screen. Proc. Natl. Acad. Sci. USA 104, 19023–19028 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Williams, A. et al. Novel targets for Huntington's disease in an mTOR-independent autophagy pathway. Nat. Chem. Biol. 4, 295–305 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Rose, C. et al. Rilmenidine attenuates toxicity of polyglutamine expansions in a mouse model of Huntington's disease. Hum. Mol. Genet. 19, 2144–2153 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Lipinski, M.M. et al. Genome-wide analysis reveals mechanisms modulating autophagy in normal brain aging and in Alzheimer's disease. Proc. Natl. Acad. Sci. USA 107, 14164–14169 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Mariño, G. et al. Tissue-specific autophagy alterations and increased tumorigenesis in mice deficient in Atg4C/autophagin-3. J. Biol. Chem. 282, 18573–18583 (2007).

    Article  PubMed  Google Scholar 

  47. Qu, X. et al. Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene. J. Clin. Invest. 112, 1809–1820 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Takahashi, Y. et al. Bif-1 interacts with Beclin 1 through UVRAG and regulates autophagy and tumorigenesis. Nat. Cell Biol. 9, 1142–1151 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. White, E., Karp, C., Strohecker, A.M., Guo, Y. & Mathew, R. Role of autophagy in suppression of inflammation and cancer. Curr. Opin. Cell Biol. 22, 212–217 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Han, J. et al. Involvement of protective autophagy in TRAIL resistance of apoptosis-defective tumor cells. J. Biol. Chem. 283, 19665–19677 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Colell, A. et al. GAPDH and autophagy preserve survival after apoptotic cytochrome c release in the absence of caspase activation. Cell 129, 983–997 (2007).

    Article  CAS  PubMed  Google Scholar 

  52. Sotelo, J., Briceno, E. & Lopez-Gonzalez, M.A. Adding chloroquine to conventional treatment for glioblastoma multiforme: a randomized, double-blind, placebo-controlled trial. Ann. Intern. Med. 144, 337–343 (2006).

    Article  CAS  PubMed  Google Scholar 

  53. Komatsu, M. & Ichimura, Y. Selective autophagy regulates various cellular functions. Genes Cells 15, 923–933 (2010).

    Article  CAS  PubMed  Google Scholar 

  54. Wullschleger, S., Loewith, R. & Hall, M.N. TOR signaling in growth and metabolism. Cell 124, 471–484 (2006).

    Article  CAS  PubMed  Google Scholar 

  55. Sancak, Y. et al. Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids. Cell 141, 290–303 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Mizushima, N. The role of the Atg1/ULK1 complex in autophagy regulation. Curr. Opin. Cell Biol. 22, 132–139 (2010).

    Article  CAS  PubMed  Google Scholar 

  57. Criollo, A. et al. The IKK complex contributes to the induction of autophagy. EMBO J. 29, 619–631 (2010).

    Article  CAS  PubMed  Google Scholar 

  58. Ravikumar, B., Duden, R. & Rubinsztein, D.C. Aggregate-prone proteins with polyglutamine and polyalanine expansions are degraded by autophagy. Hum. Mol. Genet. 11, 1107–1117 (2002).

    Article  CAS  PubMed  Google Scholar 

  59. Noda, T. & Ohsumi, Y. Tor, a phosphatidylinositol kinase homologue, controls autophagy in yeast. J. Biol. Chem. 273, 3963–3966 (1998).

    Article  CAS  PubMed  Google Scholar 

  60. Kim, D.H. et al. mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery. Cell 110, 163–175 (2002).

    Article  CAS  PubMed  Google Scholar 

  61. Klionsky, D.J. & Emr, S.D. Autophagy as a regulated pathway of cellular degradation. Science 290, 1717–1721 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Balgi, A.D. et al. Screen for chemical modulators of autophagy reveals novel therapeutic inhibitors of mTORC1 signaling. PLoS ONE 4, e7124 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  63. Feldman, M.E. et al. Active-site inhibitors of mTOR target rapamycin-resistant outputs of mTORC1 and mTORC2. PLoS Biol. 7, e38 (2009).

    Article  CAS  PubMed  Google Scholar 

  64. Thoreen, C.C. et al. An ATP-competitive mammalian target of rapamycin inhibitor reveals rapamycin-resistant functions of mTORC1. J. Biol. Chem. 284, 8023–8032 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Cantley, L.C. The phosphoinositide 3-kinase pathway. Science 296, 1655–1657 (2002).

    Article  CAS  PubMed  Google Scholar 

  66. Datta, S.R. et al. Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell 91, 231–241 (1997).

    Article  CAS  PubMed  Google Scholar 

  67. Backer, J.M. The regulation and function of Class III PI3Ks: novel roles for Vps34. Biochem. J. 410, 1–17 (2008).

    Article  CAS  PubMed  Google Scholar 

  68. Laane, E. et al. Cell death induced by dexamethasone in lymphoid leukemia is mediated through initiation of autophagy. Cell Death Differ. 16, 1018–1029 (2009).

    Article  CAS  PubMed  Google Scholar 

  69. Grandér, D., Kharaziha, P., Laane, E., Pokrovskaja, K. & Panaretakis, T. Autophagy as the main means of cytotoxicity by glucocorticoids in hematological malignancies. Autophagy 5, 1198–1200 (2009).

    Article  PubMed  Google Scholar 

  70. Alcalay, M. et al. The promyelocytic leukemia gene product (PML) forms stable complexes with the retinoblastoma protein. Mol. Cell. Biol. 18, 1084–1093 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Blommaart, E.F., Krause, U., Schellens, J.P., Vreeling-Sindelarova, H. & Meijer, A.J. The phosphatidylinositol 3-kinase inhibitors wortmannin and LY294002 inhibit autophagy in isolated rat hepatocytes. Eur. J. Biochem. 243, 240–246 (1997).

    Article  CAS  PubMed  Google Scholar 

  72. Seglen, P.O. & Gordon, P.B. 3-Methyladenine: specific inhibitor of autophagic/lysosomal protein degradation in isolated rat hepatocytes. Proc. Natl. Acad. Sci. USA 79, 1889–1892 (1982).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Raynaud, F.I. et al. Pharmacologic characterization of a potent inhibitor of class I phosphatidylinositide 3-kinases. Cancer Res. 67, 5840–5850 (2007).

    Article  CAS  PubMed  Google Scholar 

  74. Liu, Q., Thoreen, C., Wang, J., Sabatini, D. & Gray, N.S. mTOR mediated anti-cancer drug discovery. Drug Discov. Today Ther. Strateg. 6, 47–55 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Degtyarev, M. et al. Akt inhibition promotes autophagy and sensitizes PTEN-null tumors to lysosomotropic agents. J. Cell Biol. 183, 101–116 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Meley, D. et al. AMP-activated protein kinase and the regulation of autophagic proteolysis. J. Biol. Chem. 281, 34870–34879 (2006).

    Article  CAS  PubMed  Google Scholar 

  77. Meijer, A.J. & Codogno, P. AMP-activated protein kinase and autophagy. Autophagy 3, 238–240 (2007).

  78. Williams, R.S., Cheng, L., Mudge, A.W. & Harwood, A.J. A common mechanism of action for three mood-stabilizing drugs. Nature 417, 292–295 (2002).

    Article  CAS  PubMed  Google Scholar 

  79. Sarkar, S. et al. Lithium induces autophagy by inhibiting inositol monophosphatase. J. Cell Biol. 170, 1101–1111 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Hallcher, L.M. & Sherman, W.R. The effects of lithium ion and other agents on the activity of myo-inositol-1-phosphatase from bovine brain. J. Biol. Chem. 255, 10896–10901 (1980).

    Article  CAS  PubMed  Google Scholar 

  81. Inhorn, R.C. & Majerus, P.W. Properties of inositol polyphosphate 1-phosphatase. J. Biol. Chem. 263, 14559–14565 (1988).

    Article  CAS  PubMed  Google Scholar 

  82. Shaltiel, G. et al. Valproate decreases inositol biosynthesis. Biol. Psychiatry 56, 868–874 (2004).

    Article  CAS  PubMed  Google Scholar 

  83. Xia, H.G. et al. Control of basal autophagy by calpain1 mediated cleavage of ATG5. Autophagy 6, 61–66 (2010).

    Article  CAS  PubMed  Google Scholar 

  84. Roufogalis, B.D., Minocherhomjee, A.M. & Al-Jobore, A. Pharmacological antagonism of calmodulin. Can. J. Biochem. Cell Biol. 61, 927–933 (1983).

    Article  CAS  PubMed  Google Scholar 

  85. Sczekan, S.R. & Strumwasser, F. Antipsychotic drugs block IP3-dependent Ca(2+)-release from rat brain microsomes. Biol. Psychiatry 40, 497–502 (1996).

    Article  CAS  PubMed  Google Scholar 

  86. Crowe, J.H. Trehalose as a “chemical chaperone”: fact and fantasy. Adv. Exp. Med. Biol. 594, 143–158 (2007).

    Article  PubMed  Google Scholar 

  87. Sarkar, S., Davies, J.E., Huang, Z., Tunnacliffe, A. & Rubinsztein, D.C. Trehalose, a novel mTOR-independent autophagy enhancer, accelerates the clearance of mutant huntingtin and alpha-synuclein. J. Biol. Chem. 282, 5641–5652 (2007).

    Article  CAS  PubMed  Google Scholar 

  88. Rodríguez-Navarro, J.A. et al. Trehalose ameliorates dopaminergic and tau pathology in parkin deleted/tau overexpressing mice through autophagy activation. Neurobiol. Dis. 39, 423–438 (2010).

    Article  PubMed  CAS  Google Scholar 

  89. Sarkar, S. & Rubinsztein, D.C. Small molecule enhancers of autophagy for neurodegenerative diseases. Mol. Biosyst. 4, 895–901 (2008).

    Article  CAS  PubMed  Google Scholar 

  90. Bommareddy, A. et al. Atg5 regulates phenethyl isothiocyanate-induced autophagic and apoptotic cell death in human prostate cancer cells. Cancer Res. 69, 3704–3712 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Lefranc, F., Facchini, V. & Kiss, R. Proautophagic drugs: a novel means to combat apoptosis-resistant cancers, with a special emphasis on glioblastomas. Oncologist 12, 1395–1403 (2007).

    Article  CAS  PubMed  Google Scholar 

  92. Sarkar, S. et al. A rational mechanism for combination treatment of Huntington's disease using lithium and rapamycin. Hum. Mol. Genet. 17, 170–178 (2008).

    Article  CAS  PubMed  Google Scholar 

  93. Miller, S. et al. Shaping development of autophagy inhibitors with the structure of the lipid kinase Vps34. Science 327, 1638–1642 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Lu, X. et al. Designed semisynthetic protein inhibitors of Ub/Ubl E1 activating enzymes. J. Am. Chem. Soc. 132, 1748–1749 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Kumanomidou, T. et al. The crystal structure of human Atg4b, a processing and de-conjugating enzyme for autophagosome-forming modifiers. J. Mol. Biol. 355, 612–618 (2006).

    Article  CAS  PubMed  Google Scholar 

  96. Sugawara, K. et al. Structural basis for the specificity and catalysis of human Atg4B responsible for mammalian autophagy. J. Biol. Chem. 280, 40058–40065 (2005).

    Article  CAS  PubMed  Google Scholar 

  97. Hopkins, A.L. & Groom, C.R. The druggable genome. Nat. Rev. Drug Discov. 1, 727–730 (2002).

    Article  CAS  PubMed  Google Scholar 

  98. Overington, J.P., Al-Lazikani, B. & Hopkins, A.L. How many drug targets are there? Nat. Rev. Drug Discov. 5, 993–996 (2006).

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We are grateful for funding from the Medical Research Council (Programme Grant to D.C.R.; Skills Gap Award to A.F.), the Wellcome Trust (Senior Fellowship to D.C.R.), the UK National Institute for Health Research, Biomedical Research Centre at Addenbrooke's Hospital, Special Coordination Funds for Promoting Science and Technology of the Ministry of Education, Culture, Sports, Science and Technology of Japan, and the Takeda Science Foundation.

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  1. Department of Medical Genetics, University of Cambridge, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom

    Angeleen Fleming & David C Rubinsztein

  2. Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom

    Angeleen Fleming

  3. Department of Genetics, Graduate School of Medicine, Osaka University, Osaka, Japan

    Takeshi Noda & Tamotsu Yoshimori

  4. Laboratory of Intracellular Membrane Dynamics, Graduate School of Frontier Bioscience, Osaka University, Osaka, Japan

    Takeshi Noda & Tamotsu Yoshimori

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  1. Angeleen Fleming
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Correspondence to Tamotsu Yoshimori or David C Rubinsztein.

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David Rubinsztein is an inventor on patents describing autophagy-inducing drugs as potential therapeutics.

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Fleming, A., Noda, T., Yoshimori, T. et al. Chemical modulators of autophagy as biological probes and potential therapeutics. Nat Chem Biol 7, 9–17 (2011). https://doi.org/10.1038/nchembio.500

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