Skip to main content
SpringerLink
Log in

Autophagy and Self-Defense

  • Chapter
Self and Nonself

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 738))

Abstract

Autophagy is a highly conserved mechanism which is essential for the maintenance of cellular homeostasis in response to cellular stress. Autophagy has been conserved from yeast to humans as a quality control process that is involved in the recognition and turnover of damaged proteins and organelles. It is also a response mechanism to nutrient starvation. In mammals, autophagy is involved in antigen presentation, tolerance, inflammation and protection against neurodegenerative diseases. The decrease of autophagy during aging reduces the removal of damaged organelles and increases the accumulation of waste products in the cells. In this chapter, we review these aspects of autophagy along with their role in self-nonself distinction, their implication in innate and adaptive immune response, and its dysregulation in the pathology of certain inflammatory and autoimmune diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Lum JJ, DeBerardinis RJ, Thompson CB. Autophagy in metazoans: cell survival in the land of plenty. Nat Rev Mol Cell Biol 2005; 6:439–448.

    Article  PubMed  CAS  Google Scholar 

  2. Kuma A, Hatano M, Matsui M et al. The role of autophagy during the early neonatal starvation period. Nature 2004; 432:1032–1036.

    Article  PubMed  CAS  Google Scholar 

  3. Komatsu M, Waguri S, Ueno T et al. Impairment of starvation-induced and constitutive autophagy in Atg7-deficient mice. J Cell Biol 2005; 169:425–434.

    Article  PubMed  CAS  Google Scholar 

  4. Cuervo AM, Bergamini E, Brunk UT et al. Autophagy andaging. Autophagy 2005; 1:131–140.

    Article  PubMed  Google Scholar 

  5. Martinez-Vicente M, Cuervo AM. Autophagy and neurodegeneration: when the cleaning crew goes on strike. Lancet Neurol 2007; 6:352–361.

    Article  PubMed  CAS  Google Scholar 

  6. Gottlieb RA, Mentzer RM. Autophagy during cardiac stress: Joys and Frustrations. Annu Rev Physiol 2010; 72:45–59.

    Article  PubMed  CAS  Google Scholar 

  7. Yang Z, Klionsky DJ. Mammalian autophagy: core molecular machinery and signaling regulation. Curr Opin Cell Biol 2010; 22:124–131.

    Article  PubMed  CAS  Google Scholar 

  8. Chan EY, Tooze SA. Evolution of Atg1 function and regulation. Autophagy 2009; 5:758–765.

    PubMed  CAS  Google Scholar 

  9. Jung CH, Jun CB, Ro S-H et al. ULK-Atg13-FiP200 complexes mediate mTOR signaling to the autophagy machinery. Mol Biol Cell 2009; 20:1992–2003.

    Article  PubMed  CAS  Google Scholar 

  10. Levine B, Sinha S, Kroemer G. Bcl-2 family members: dual regulators of apoptosis and autophagy. Autophagy 2008; 4:600–606.

    PubMed  CAS  Google Scholar 

  11. Nakatogawa H, Ichimura Y, Ohsumi Y. Atg8, a ubiquitin-like protein required for autophagosome formation, mediates membrane tethering and hemifusion. Cell 2007; 130:165–178.

    Article  PubMed  CAS  Google Scholar 

  12. Sou Y-S, Waguri S, Iwata J et al. The Atg8 conjugation system is indispensable for proper development of autophagic isolation membranes in mice. Mol Biol Cell 2008; 19:4762–4775.

    Article  PubMed  CAS  Google Scholar 

  13. Young ARJ, chang EYW, Hu XW et al. Starvation and ULK1-dependent cycling of Mammalian Atg9 between the TGN and Endosomes. J Cell Sci 2006; 119:3888–3900.

    Article  PubMed  CAS  Google Scholar 

  14. Webber JL, Young ARJ, Tooze SA. Atg9 trafficking in mammalian cells. Autophagy 2007; 3:54–56.

    PubMed  CAS  Google Scholar 

  15. Webber JL, Tooze SA. New insights into the function of Atg9. FEBS Lett 2010; 584:1319–1326.

    Article  PubMed  CAS  Google Scholar 

  16. Komatsu M, Waguri S, Chiva T et al. Loss of autophagy in the central nervous system causes neurodegeneration in mice. Nature 2006; 441:880–884.

    Article  PubMed  CAS  Google Scholar 

  17. Hara T, Nakamura Km Matsui M, Yamamoto A et al. Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature 2006; 441:885–889.

    Article  PubMed  CAS  Google Scholar 

  18. He C, Klionsky DJ. Regulation mechanisms and signaling pathways of autophagy. Annu Rev Genet 2009; 43:67–93.

    Article  PubMed  CAS  Google Scholar 

  19. Mehrpour M, Esclatine A, Beau I et al. Autophagy in health and disease. 1. Regulation and significance of autophagy: an overview. Am J Physiol Cell Physiol 2010; 298:C776–C785.

    Article  PubMed  CAS  Google Scholar 

  20. Jung CH, Ro S-H, Cao J et al. mTOR regulation of autophagy. FEBS Lett 2010; 584:1287–1295.

    Article  PubMed  CAS  Google Scholar 

  21. Chan EYW, Longatti A, McKnight NC et al. Kinase-inactivated ULK proteins inhibit autophagy via their conserved C-terminal domains using an Atg13-independent mechanism. Mol Cell Biol 2009; 29:157–171.

    Article  PubMed  CAS  Google Scholar 

  22. Hosokaway N, Hara T, Kaizuka T et al. Nutrient-dependent mTORC1 association with the ULK1-Atg13-FIP200 complex required for autophagy. Mol Biol Cell 2009; 20:1981–1991.

    Article  Google Scholar 

  23. Shi C-S, Kehrl JH. MyD88 and Trif target Beclin 1 to trigger autophagy in macrophages. J Biol Chem 2008; 283:33175–33182.

    Article  PubMed  CAS  Google Scholar 

  24. Kim E, Goraksha-Hicks P, Li L et al. Regulation of TORC1 by Rag GTPases in nutrient response. Nat Cell Biol 2008; 10:935–945.

    Article  PubMed  CAS  Google Scholar 

  25. Sancak Y, Peterson TR, Shaul YD et al. The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1. Science 2008; 320:1496–1501.

    Article  PubMed  CAS  Google Scholar 

  26. Nobukuni T, Joaquin M, Roccio M et al. Amino acids mediate mTOR/raptor signaling through activation of class 3 phosphatidylinositol 3OH-kinase. Proc Natl Acad USA 2005; 102:14238–14243.

    Article  CAS  Google Scholar 

  27. Inoki K, Zhu T, Guan K-L. TSC2 regulates cellular energy response to control cell growth and survival. Cell 2003; 115:577–590.

    Article  PubMed  CAS  Google Scholar 

  28. Horak P, Crawford AR, Vadysirisack DD et al. Negative feedback control of HIF-1 through REDD1-regulated ROS suppresses tumorigenesis. Proc Nat Acad Sci USA 2010; 107:4675–4680.

    Article  PubMed  CAS  Google Scholar 

  29. Sofer A, Lei K, Johannessen CM et al. Regulation of mTOR and cell growth in response to energy stress by REDD1. Mol Cell Biol 2005; 25:5834–5845.

    Article  PubMed  CAS  Google Scholar 

  30. Chen JL, Lin HH, Kim KJ et al. Novel roles for protein kinase Cd-dependent signaling pathways in acute hypoxic stress-induced autophagy. J Biol Chem 2008; 283:34432–34444.

    Article  PubMed  CAS  Google Scholar 

  31. Ding W-X, Yin X-M. Sorting, recognition and activation of the misfolded protein degradation pathways through macroautophagy and the proteasome. Autophagy 2008; 4:141–150.

    PubMed  CAS  Google Scholar 

  32. Ogata M, Hino S, Saito A et al. Autophagy is activated for cell survival after endoplasmic reticulum stress. Mol Cell Biol 2006; 26:9220–9231.

    Article  PubMed  CAS  Google Scholar 

  33. Ding WX, Ni HM, Gao W et al. Linking of autophagy to ubiquitin-Proteasome system is important for the regulation of endoplasmic reticulum stress and cell viability. Am J Pathol 2007; 171:513–524.

    Article  PubMed  CAS  Google Scholar 

  34. Hoyer-Hansen M, Bastholm L, Szyniarowski P et al. Control for macroautophagy by calcium, calmodulin-dependent kinase kinase-b and Bcl-2. Mol Cell 2007; 25:193–205.

    Article  PubMed  Google Scholar 

  35. Fimia GM, Piacentini M. Regulation of autophagy in mammals and its interplay with apoptosis. Cell Mol Lif Sci 2010; 67:1581–1588.

    Article  CAS  Google Scholar 

  36. Kroemer G, Levine B. Autophagic cell death: the story of a misnomer. Nat Rev Mol Cell Biol 2008; 9:1004–1010.

    Article  PubMed  CAS  Google Scholar 

  37. Kroemer G, Galluzzi L, Brenner C. Mitochondrial membrane permeabilization in cell death. Physiol Rev 2007; 87:99–163.

    Article  PubMed  CAS  Google Scholar 

  38. Salminen A, Kaarniranta K. Regulation of theaging process by autophagy. Trends Mol Med 2009; 15:217–224.

    Article  PubMed  CAS  Google Scholar 

  39. Madeo F, Tavernarakis N, Kroemer G. Can autophagy promote longevity? Nat Cell Biol 2010; 12:842–846.

    Article  PubMed  CAS  Google Scholar 

  40. Hars ES, Qi H, Ryazanov AG et al. Autophagy regulates aging in C. elegans. Autophagy 2005; 3:93–95.

    Google Scholar 

  41. Lee IH, Cao L, Mostoslavsky R et al. A role for the NAD-dependent deacetylase Sirt1 in the regulation of autophagy. Proc Natl Acad Sci USA 2008; 105:3374–3379.

    Article  PubMed  CAS  Google Scholar 

  42. Tavernarakis N, Pasparaki A, Tasdemir E et al. The effects of p53 on whole organism longevity are mediated by autophagy. Autophagy 2008; 4:870–873.

    PubMed  CAS  Google Scholar 

  43. Tasdemir E, Maiuri MC, Galluzzi L et al. Regulation of autophagy by cytoplasmic p53. Nat Cell Biol 2008; 6:676–687.

    Article  Google Scholar 

  44. Mariño G, Fernandez AF, Cabrera S et al. Autophagy is essential for mouse sense of balance. J Clin Invest 2010; 120:2331–2344.

    Article  PubMed  Google Scholar 

  45. Virgin HW, Levine B. Autophagy genes in immunity. Nat Immunol 2009; 10:461–470.

    Article  PubMed  CAS  Google Scholar 

  46. Deretic V, Levine B. Autophagy, immunity and microbial adaptations. Cell Host Microbe 2009; 5:527–549.

    Article  PubMed  CAS  Google Scholar 

  47. Saitoh T, Akira S. Regulation of innate immune responses by autophagy-related proteins. J Cell Biol 2010; 189:925–935.

    Article  PubMed  CAS  Google Scholar 

  48. Sanjuan MA, Milasta S, Green DR. Toll-like receptor signaling in the lysosomal pathways. Immunol Rev 2009; 227:203–220.

    Article  PubMed  CAS  Google Scholar 

  49. Sanjuan MA, Dillon CP, Tait SWG et al. Toll-like receptor signaling in macrophages links the autophagy pathway to phagocytosis. Nature 2007; 450:1253–1257.

    Article  PubMed  CAS  Google Scholar 

  50. Xu Y, Jagannath C, Liu X-D et al. Toll-like receptor 4 is sensor for autophagy associated with innate immunity. Immunity 2007; 27:135–144.

    Article  PubMed  CAS  Google Scholar 

  51. Delgado MA, Elmaoued RA, Davis AS et al. Toll-like receptors control autophagy. EMBO J 2008; 27:1110–1121.

    Article  PubMed  CAS  Google Scholar 

  52. Orvedahl A, Alexander D, Tallóczy Z et al. HSV-1 ICP34.5 confers neurovirulence by targeting the Beclin 1 autophagy protein. Cell Host Microbe 2007; 1:23–35.

    Article  PubMed  CAS  Google Scholar 

  53. Ogawa M, Yoshimori T, Suzuki T et al. Esape of Intracellular Shigella from Autophagy. Science 2005; 307:727–731.

    Article  PubMed  CAS  Google Scholar 

  54. Birmingham CL, Smith AC, Bakowski MA et al. Autophagy controls Salmonella infection in response to damage to the Salmonella-containing vacuole. J Biol Chem 2006; 281:11374–11383.

    Article  PubMed  CAS  Google Scholar 

  55. Lee HK, Lund JM, Ramanathan B et al. Autophagy-dependent viral recognition by plasmacytoid dendritic cells. Science 2007; 315:1398–1401.

    Article  PubMed  CAS  Google Scholar 

  56. Lande R, Gilliet M. Plasmacytoid dendritic cells: key players in the initiation and regulation of immune responses. Ann N Y Acad Sci 2010; 1183:89–102.

    Article  PubMed  CAS  Google Scholar 

  57. Avalos AM, Busconi L, Marshak-Rothstein A. Regulation of autoreactive B cell responses to endogenous TLR ligands. Autoimmunity 2010; 43:76–83.

    Article  PubMed  CAS  Google Scholar 

  58. Monroe JG, Keir ME. Bridging Toll-like-and B Cell-receptor signaling: meet me at the autophagosome. Immunity 2008; 28:729–731.

    Article  PubMed  CAS  Google Scholar 

  59. Chaturvedi A, Dorward D, Pierce SK. The B cell receptor governs the subcellular location of Toll-like receptor 9 leading to hyperresponses to DNA-containing antigens. Immunity 2008; 28:799–809.

    Article  PubMed  CAS  Google Scholar 

  60. Chen G, Shaw M, Kim Y-G et al. NOD-like receptors: role in innate immunity and inflammatory disease. Annu Rev Pathol 2009; 4:365–398.

    Article  PubMed  CAS  Google Scholar 

  61. Franchi L, Warner N, Viani K et al. Function of Nod-like receptors in microbial recognition and host defense. Immunol Rev 2009; 227:106–128.

    Article  PubMed  CAS  Google Scholar 

  62. Ogura Y, Bonen DK, Inohara N et al. A frameshift mutation in NOD2 associated with susceptibility to Crohn’s disease. Nature 2001; 411:603–606.

    Article  PubMed  CAS  Google Scholar 

  63. Hugot J-P, Chamaillard M, Zouali H et al. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn’s disease. Nature 2001; 411:599–603.

    Article  PubMed  CAS  Google Scholar 

  64. McGovern DPB, Hysi P, Ahmad T et al. Association between a complex insertion/deletion polymorphism in NOD1 (CARD4) and susceptibility to inflammatory bowel disease. Hum Mol Genet 2005; 14:1245–1250.

    Article  PubMed  CAS  Google Scholar 

  65. Travassos LH, Caneiro LAM, Ramjeet M et al. Nod1 and Nod2 direct autophagy by recruiting ATG16L1 to the plasma membrane at the site of bacterial entry. Nat Immunol 2010; 11:55–63.

    Article  PubMed  CAS  Google Scholar 

  66. Hampe J, Franke A, Rosenstiel P et al. A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1. Nat Genet 2007; 39:207–211.

    Article  PubMed  CAS  Google Scholar 

  67. Rioux JD, Xavier RJ, Taylor KD et al. Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis. Nat Genet 2007; 39:596–604.

    Article  PubMed  CAS  Google Scholar 

  68. Crotzer VL, Blum JS. Autophagy and its role in MHC-mediated antigen presentation. J Immunol 2009; 182:3335–3341.

    Article  PubMed  CAS  Google Scholar 

  69. Vyas JM, Van der Veen AG, Ploegh HL. The known unknowns of antigen processing and presentation. Nat Rev Immunol 2008; 8:607–618.

    Article  PubMed  CAS  Google Scholar 

  70. Li Y, Wan L-X, Yang G et al. Efficient cross-presentation depends on autophagy in tumor cells. Cancer Res 2008; 68:6889–6895.

    Article  PubMed  CAS  Google Scholar 

  71. Andrade RM, Wessendarp M, Gubbels M-J et al. CD40 induces macrophage anti-Toxoplasma gondii activity by triggering autophagy-dependent fusion of pathogen-containing vacuoles and lysosomes. J Clin Invest 2006; 2366–2377.

    Google Scholar 

  72. Luder CG, Seeber F. Toxoplasma gondii and MHC-restricted antigen presentation: on degradation, transport and modulation. Int J Parasitol 2001; 31:1355–1369.

    Article  PubMed  CAS  Google Scholar 

  73. Schmid D, Pypaert M, Munz C. Antigen-loading compartments for major histocompatibility complex class II molecules continuously receive input from autophagosomes. Immunity 2007; 26:79–92.

    Article  PubMed  CAS  Google Scholar 

  74. Menendez-Benito V, Neefjes J. Autophagy in MHC class II presentation: sampling from within. Immunity 2007; 26:1–3.

    Article  PubMed  CAS  Google Scholar 

  75. Nedjic J, Aichinger M, Emmerich J et al. Autophagy in thymic epithelium shapes the T-cell repertoire and is essential for tolerance. Nature 2008; 455:396–400.

    Article  PubMed  CAS  Google Scholar 

  76. Nakagawa I, Amano A, Mizushima N et al. Autophagy defends cells against invading group A Streptococcus. Science 2004; 306:1037–1040.

    Article  PubMed  CAS  Google Scholar 

  77. Gutierrez MG, Master SS, Singh SB et al. Autophagy is a defense mechanism inhibiting BCG and Mycobacterium tuberculosis survival in infected macrophages. Cell 2004; 119:753–766.

    Article  PubMed  CAS  Google Scholar 

  78. Tallóczy Z, Virgin HW, Levine B. PKR-dependent autophagic degradation of herpex simplex virus Type 1. Autophagy 2006; 2:24–29.

    PubMed  Google Scholar 

  79. Ait-Goughoulte M, Kanda T, Meyer K et al. Hepatitis C virus genotype 1a growth and induction of autophagy. J Virol 2008; 82:2241–2249.

    Article  PubMed  CAS  Google Scholar 

  80. Kyei GB, Dinkins C, Davis AS et al. Autophagy pathway intersects with HIV-1 biosynthesis and regulates viral yields in macrophages. J Cell Biol 2009; 186:255–268.

    Article  PubMed  CAS  Google Scholar 

  81. Blanchet FP, Moris A, Nikolic DS et al. Human immunodeficiency Virus-1 inhibition of immunoamphisomes in dendritic cells impair early innate and adaptive immune responses. Immunity 2010; 32:654–669.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Immunology Department, Hospital Universitario Central de Asturias, Oviedo, Spain

    Jesús Martínez-Borra & Carlos López-Larrea

  2. Fundación Renal “Iñigo Álvarez de Toledo,”, Madrid, Spain

    Carlos López-Larrea

Authors
  1. Jesús Martínez-Borra
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Carlos López-Larrea
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Carlos López-Larrea .

Editor information

Editors and Affiliations

  1. Department of Immunology, Hospital Universitario Central de Asturias, Oviedo, Spain

    Carlos López-Larrea PhD

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Landes Bioscience and Springer Science+Business Media

About this chapter

Cite this chapter

Martínez-Borra, J., López-Larrea, C. (2012). Autophagy and Self-Defense. In: López-Larrea, C. (eds) Self and Nonself. Advances in Experimental Medicine and Biology, vol 738. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-1680-7_11

Download citation

Publish with us

Policies and ethics

Search

Navigation