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Front Cell Dev Biol. 2018 Nov 27;6:160. doi: 10.3389/fcell.2018.00160. eCollection 2018.

Chemical Biology Strategies to Study Autophagy.

Frontiers in cell and developmental biology

Piyush Mishra, Veena Ammanathan, Ravi Manjithaya

Affiliations

  1. Autophagy Lab, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bengaluru, India.

PMID: 30538986 PMCID: PMC6277461 DOI: 10.3389/fcell.2018.00160

Abstract

Growing amount of evidence in the last two decades highlight that macroautophagy (generally referred to as autophagy) is not only indispensable for survival in yeast but also equally important to maintain cellular quality control in higher eukaryotes as well. Importantly, dysfunctional autophagy has been explicitly shown to be involved in various physiological and pathological conditions such as cell death, cancer, neurodegenerative, and other diseases. Therefore, modulation and regulation of the autophagy pathway has emerged as an alternative strategy for the treatment of various disease conditions in the recent years. Several studies have shown genetic or pharmacological modulation of autophagy to be effective in treating cancer, clearing intracellular aggregates and pathogens. Understanding and controlling the autophagic flux, either through a genetic or pharmacological approach is therefore a highly promising approach and of great scientific interest as spatiotemporal and cell-tissue-organ level autophagy regulation is not clearly understood. Indeed, chemical biology approaches that identify small molecule effectors of autophagy have thus a dual benefit: the modulators act as tools to study and understand the process of autophagy, and may also have therapeutic potential. In this review, we discuss different strategies that have appeared to screen and identify potent small molecule modulators of autophagy.

Keywords: autophagy; chemical biology; fluorescence microscopy; high throughput; luciferase; small molecule screening

References

  1. mSphere. 2016 Mar 02;1(2):null - PubMed
  2. Annu Rev Nutr. 2007;27:19-40 - PubMed
  3. J Biomol Screen. 2015 Aug;20(7):913-20 - PubMed
  4. Sci Data. 2018 Jun 26;5:180116 - PubMed
  5. Cell. 1993 May 7;73(3):585-96 - PubMed
  6. J Biol Chem. 2004 Sep 10;279(37):39068-74 - PubMed
  7. Autophagy. 2010 Aug;6(6):794-7 - PubMed
  8. J Cell Biol. 2016 Dec 19;215(6):857-874 - PubMed
  9. Nat Rev Mol Cell Biol. 2007 Nov;8(11):931-7 - PubMed
  10. FEBS Lett. 2002 Aug 28;526(1-3):71-6 - PubMed
  11. Nat Genet. 2004 Jun;36(6):585-95 - PubMed
  12. Biochem Biophys Rep. 2017 Jul 20;11:138-146 - PubMed
  13. Autophagy. 2017 Sep 2;13(9):1556-1572 - PubMed
  14. Methods Enzymol. 2017;588:413-427 - PubMed
  15. J Biol Chem. 2011 Nov 11;286(45):38904-12 - PubMed
  16. Genetics. 2011 Dec;189(4):1177-201 - PubMed
  17. Biochem Biophys Res Commun. 1995 May 5;210(1):126-32 - PubMed
  18. FEBS Lett. 1994 Aug 1;349(2):275-80 - PubMed
  19. Trends Microbiol. 2013 Sep;21(9):451-6 - PubMed
  20. Autophagy. 2007 Mar-Apr;3(2):106-16 - PubMed
  21. Science. 2010 Dec 3;330(6009):1344-8 - PubMed
  22. FEBS Lett. 1993 Oct 25;333(1-2):169-74 - PubMed
  23. Methods Mol Biol. 2015;1270:155-65 - PubMed
  24. Biochim Biophys Acta. 2006 Dec;1763(12):1767-75 - PubMed
  25. Nat Chem Biol. 2007 Jun;3(6):331-8 - PubMed
  26. Drug Discov Today Technol. 2013 Spring;10(1):e137-44 - PubMed
  27. PLoS One. 2009 Sep 22;4(9):e7124 - PubMed
  28. Nat Cell Biol. 2013 Jul;15(7):713-20 - PubMed
  29. Cells. 2017 Jul 13;6(3):null - PubMed
  30. Autophagy. 2009 May;5(4):511-9 - PubMed
  31. Proc Natl Acad Sci U S A. 1982 Mar;79(6):1889-92 - PubMed
  32. EMBO Mol Med. 2014 Dec 22;7(2):127-39 - PubMed
  33. Autophagy. 2017 Jul 3;13(7):1221-1234 - PubMed
  34. Nat Rev Drug Discov. 2012 Sep;11(9):709-30 - PubMed
  35. J Biol Chem. 1998 Feb 13;273(7):3963-6 - PubMed
  36. EMBO J. 2000 Nov 1;19(21):5720-8 - PubMed
  37. Autophagy. 2016;12(1):1-222 - PubMed
  38. Autophagy. 2013 Sep;9(9):1407-17 - PubMed
  39. J Cell Biol. 1999 Oct 18;147(2):435-46 - PubMed
  40. Methods Enzymol. 2008;451:1-26 - PubMed
  41. EMBO J. 2001 Nov 1;20(21):5971-81 - PubMed
  42. Annu Rev Immunol. 1996;14:483-510 - PubMed
  43. Annu Rev Physiol. 1966;28:435-92 - PubMed
  44. Autophagy. 2010 Aug;6(6):784-93 - PubMed
  45. EMBO J. 2012 Jun 29;31(13):2852-68 - PubMed
  46. J Cell Biol. 2005 Nov 21;171(4):603-14 - PubMed
  47. BMC Biol. 2011 Jun 02;9:38 - PubMed
  48. Autophagy. 2008 Aug;4(6):801-6 - PubMed
  49. Autophagy. 2010 Nov;6(8):1204-5 - PubMed
  50. Biochem Soc Trans. 2013 Oct;41(5):1103-30 - PubMed
  51. Biochem Biophys Res Commun. 2011 Jan 28;404(4):1039-43 - PubMed
  52. Proc Natl Acad Sci U S A. 2004 Nov 23;101(47):16594-9 - PubMed
  53. Nat Chem Biol. 2006 Feb;2(2):103-9 - PubMed
  54. J Am Chem Soc. 2011 May 4;133(17):6642-9 - PubMed
  55. J Bacteriol. 1995 Jan;177(2):357-63 - PubMed
  56. J Clin Invest. 2015 Jan;125(1):1-4 - PubMed
  57. Nat Chem Biol. 2015 May;11(5):347-354 - PubMed
  58. Autophagy. 2007 Nov-Dec;3(6):542-5 - PubMed
  59. Autophagy. 2007 Sep-Oct;3(5):452-60 - PubMed
  60. Genes Cells. 2010 Sep 1;15(9):923-33 - PubMed
  61. Front Mol Neurosci. 2018 Apr 09;11:109 - PubMed
  62. J Biol Chem. 1998 Dec 18;273(51):33889-92 - PubMed
  63. Proc Natl Acad Sci U S A. 2015 Aug 4;112(31):E4281-7 - PubMed
  64. J Cell Biol. 1995 Nov;131(3):591-602 - PubMed
  65. Cells. 2017 Jul 07;6(3):null - PubMed
  66. Mol Cell. 2015 Jul 16;59(2):285-97 - PubMed
  67. Proc Natl Acad Sci U S A. 2007 Nov 27;104(48):19023-8 - PubMed
  68. J Cell Biol. 1992 Oct;119(2):301-11 - PubMed
  69. Nat Chem Biol. 2008 May;4(5):295-305 - PubMed
  70. J Cell Biol. 1967 Nov;35(2):C11-6 - PubMed
  71. Mol Cell. 2016 Nov 17;64(4):835-849 - PubMed
  72. Nat Commun. 2015 Oct 27;6:8620 - PubMed
  73. Curr Chem Genom Transl Med. 2014 Feb 07;8(Suppl 1):3-15 - PubMed
  74. Mol Biol Cell. 2004 Mar;15(3):1101-11 - PubMed
  75. Exp Cell Res. 2018 Feb 1;363(1):84-94 - PubMed
  76. Mol Biosyst. 2008 Sep;4(9):895-901 - PubMed
  77. EMBO J. 2010 Jun 2;29(11):1792-802 - PubMed

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