Journal of the Indian Institute of Science

, Volume 97, Issue 1, pp 79–94 | Cite as

Multifaceted Housekeeping Functions of Autophagy

  • Sarika Chinchwadkar
  • Sreedevi Padmanabhan
  • Piyush Mishra
  • Sunaina Singh
  • S. N. Suresh
  • Somya Vats
  • Gaurav Barve
  • Veena Ammanathan
  • Ravi ManjithayaEmail author
Review Article


Autophagy is an evolutionarily conserved intracellular degradation process in which cytoplasmic components are captured in double membrane vesicles called autophagosomes and delivered to lysosomes for degradation. This process has an indispensable role in maintaining cellular homeostasis. The rate at which the dynamic turnover of cellular components takes place via the process of autophagy is called autophagic flux. In this review, we discuss about the orchestrated events in the autophagy process, transcriptional regulation, role of autophagy in some major human diseases like cancer, neurodegeneration (aggrephagy), and pathogenesis (xenophagy). In addition, autophagy has non-canonical roles in protein secretion, thus demonstrating the multifaceted role of autophagy in intracellular processes.


Autophagosome Formation Autophagy Gene Autophagy Protein Autophagy Machinery Lysosome Biogenesis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Mizushima N, Yoshimori T, Ohsumi Y (2011) The role of Atg proteins in autophagosome formation. Annu Rev Cell Dev Biol 27:107–132CrossRefGoogle Scholar
  2. 2.
    Takeshige K, Baba M, Tsuboi S, Noda T, Ohsumi Y (1992) Autophagy in yeast demonstrated with proteinase-deficient mutants and conditions for its induction. J Cell Biol 119:301–311CrossRefGoogle Scholar
  3. 3.
    Noda T, Ohsumi Y (1998) Tor, a phosphatidylinositol kinase homologue, controls autophagy in yeast. J Biol Chem 273:3963–3966CrossRefGoogle Scholar
  4. 4.
    Kamada Y et al (2000) Tor-mediated induction of autophagy via an Apg1 protein kinase complex. J Cell Biol 150:1507–1513CrossRefGoogle Scholar
  5. 5.
    Suzuki K, Kubota Y, Sekito T, Ohsumi Y (2007) Hierarchy of Atg proteins in pre-autophagosomal structure organization. Genes Cells 12:209–218CrossRefGoogle Scholar
  6. 6.
    Yamamoto H et al (2016) The intrinsically disordered protein Atg13 mediates supramolecular assembly of autophagy initiation complexes. Dev Cell 38:86–99CrossRefGoogle Scholar
  7. 7.
    Ragusa MJ, Stanley RE, Hurley JH (2012) Architecture of the Atg17 complex as a scaffold for autophagosome biogenesis. Cell 151:1501–1512CrossRefGoogle Scholar
  8. 8.
    Reggiori F, Ungermann C (2012) A dimer to bridge early autophagosomal membranes. Cell 151:1403–1405CrossRefGoogle Scholar
  9. 9.
    Rao Y, Perna MG, Hofmann B, Beier V, Wollert T (2016) The Atg1-kinase complex tethers Atg9-vesicles to initiate autophagy. Nat Commun 7:10338CrossRefGoogle Scholar
  10. 10.
    He C et al (2006) Recruitment of Atg9 to the preautophagosomal structure by Atg11 is essential for selective autophagy in budding yeast. J Cell Biol 175:925–935CrossRefGoogle Scholar
  11. 11.
    Reggiori F, Shintani T, Nair U, Klionsky DJ (2005) Atg9 cycles between mitochondria and the pre-autophagosomal structure in yeasts. Autophagy 1:101–109CrossRefGoogle Scholar
  12. 12.
    Backues SK et al (2015) Atg23 and Atg27 act at the early stages of Atg9 trafficking in S. cerevisiae. Traffic 16:172–190CrossRefGoogle Scholar
  13. 13.
    Reggiori F, Tucker KA, Stromhaug PE, Klionsky DJ (2004) The Atg1–Atg13 complex regulates Atg9 and Atg23 retrieval transport from the pre-autophagosomal structure. Dev Cell 6:79–90CrossRefGoogle Scholar
  14. 14.
    Obara K, Sekito T, Niimi K, Ohsumi Y (2008) The Atg18–Atg2 complex is recruited to autophagic membranes via phosphatidylinositol 3-phosphate and exerts an essential function. J Biol Chem 283:23972–23980CrossRefGoogle Scholar
  15. 15.
    Graef M, Friedman JR, Graham C, Babu M, Nunnari J (2013) ER exit sites are physical and functional core autophagosome biogenesis components. Mol Biol Cell 24:2918–2931CrossRefGoogle Scholar
  16. 16.
    Kirisako T et al (1999) Formation process of autophagosome is traced with Apg8/Aut7p in yeast. J Cell Biol 147:435–446CrossRefGoogle Scholar
  17. 17.
    Reggiori F, Klionsky DJ (2013) Autophagic processes in yeast: mechanism, machinery and regulation. Genetics 194:341–361CrossRefGoogle Scholar
  18. 18.
    Nakatogawa H, Ichimura Y, Ohsumi Y (2007) Atg8, a ubiquitin-like protein required for autophagosome formation, mediates membrane tethering and hemifusion. Cell 130:165–178CrossRefGoogle Scholar
  19. 19.
    Yao Z, Delorme-Axford E, Backues SK, Klionsky DJ (2015) Atg41/Icy2 regulates autophagosome formation. Autophagy 11:2288–2299CrossRefGoogle Scholar
  20. 20.
    Cebollero E et al (2012) Phosphatidylinositol-3-phosphate clearance plays a key role in autophagosome completion. Curr Biol 22:1545–1553CrossRefGoogle Scholar
  21. 21.
    Haas A, Scheglmann D, Lazar T, Gallwitz D, Wickner W (1995) The GTPase Ypt7p of Saccharomyces cerevisiae is required on both partner vacuoles for the homotypic fusion step of vacuole inheritance. EMBO J 14:5258–5270Google Scholar
  22. 22.
    Mayer A, Wickner W (1997) Docking of yeast vacuoles is catalyzed by the Ras-like GTPase Ypt7p after symmetric priming by Sec18p (NSF). J Cell Biol 136:307–317CrossRefGoogle Scholar
  23. 23.
    Haas A, Wickner W (1996) Homotypic vacuole fusion requires Sec17p (yeast alpha-SNAP) and Sec18p (yeast NSF). EMBO J 15:3296–3305Google Scholar
  24. 24.
    Rieder SE, Emr SD (1997) A novel RING finger protein complex essential for a late step in protein transport to the yeast vacuole. Mol Biol Cell 8:2307–2327CrossRefGoogle Scholar
  25. 25.
    Seals DF, Eitzen G, Margolis N, Wickner WT, Price A (2000) A Ypt/Rab effector complex containing the Sec1 homolog Vps33p is required for homotypic vacuole fusion. Proc Natl Acad Sci USA 97:9402–9407CrossRefGoogle Scholar
  26. 26.
    Wurmser AE, Sato TK, Emr SD (2000) New component of the vacuolar class C-Vps complex couples nucleotide exchange on the Ypt7 GTPase to SNARE-dependent docking and fusion. J Cell Biol 151:551–562CrossRefGoogle Scholar
  27. 27.
    Darsow T, Rieder SE, Emr SD (1997) A multispecificity syntaxin homologue, Vam3p, essential for autophagic and biosynthetic protein transport to the vacuole. J Cell Biol 138:517–529CrossRefGoogle Scholar
  28. 28.
    Sato TK, Darsow T, Emr SD (1998) Vam7p, a SNAP-25-like molecule, and Vam3p, a syntaxin homolog, function together in yeast vacuolar protein trafficking. Mol Cell Biol 18:5308–5319CrossRefGoogle Scholar
  29. 29.
    Wang CW, Stromhaug PE, Shima J, Klionsky DJ (2002) The Ccz1-Mon1 protein complex is required for the late step of multiple vacuole delivery pathways. J Biol Chem 277:47917–47927CrossRefGoogle Scholar
  30. 30.
    Epple UD, Suriapranata I, Eskelinen EL, Thumm M (2001) Aut5/Cvt17p, a putative lipase essential for disintegration of autophagic bodies inside the vacuole. J Bacteriol 183:5942–5955CrossRefGoogle Scholar
  31. 31.
    Teter SA et al (2001) Degradation of lipid vesicles in the yeast vacuole requires function of Cvt17, a putative lipase. J Biol Chem 276:2083–2087CrossRefGoogle Scholar
  32. 32.
    Nakamura N, Matsuura A, Wada Y, Ohsumi Y (1997) Acidification of vacuoles is required for autophagic degradation in the yeast, Saccharomyces cerevisiae. J Biochem 121:338–344CrossRefGoogle Scholar
  33. 33.
    Suriapranata I et al (2000) The breakdown of autophagic vesicles inside the vacuole depends on Aut4p. J Cell Sci 113(Pt 22):4025–4033Google Scholar
  34. 34.
    Tooze SA, Yoshimori T (2010) The origin of the autophagosomal membrane. Nat Cell Biol 12:831–835CrossRefGoogle Scholar
  35. 35.
    Bento CF et al (2016) Mammalian autophagy: how does it work? Annu Rev Biochem 85:685–713CrossRefGoogle Scholar
  36. 36.
    Yamamoto H et al (2012) Atg9 vesicles are an important membrane source during early steps of autophagosome formation. J Cell Biol 198:219–233CrossRefGoogle Scholar
  37. 37.
    Mizushima N, Yoshimori T, Levine B (2010) Methods in mammalian autophagy research. Cell 140:313–326CrossRefGoogle Scholar
  38. 38.
    Walczak M, Martens S (2013) Dissecting the role of the Atg12–Atg5–Atg16 complex during autophagosome formation. Autophagy 9:424–425CrossRefGoogle Scholar
  39. 39.
    Mizushima N et al (1998) A protein conjugation system essential for autophagy. Nature 395:395–398CrossRefGoogle Scholar
  40. 40.
    Tanida I, Ueno T, Kominami E (2004) LC3 conjugation system in mammalian autophagy. Int J Biochem Cell Biol 36:2503–2518CrossRefGoogle Scholar
  41. 41.
    Pankiv S et al (2007) p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy. J Biol Chem 282:24131–24145CrossRefGoogle Scholar
  42. 42.
    Itakura E, Kishi-Itakura C, Mizushima N (2012) The hairpin-type tail-anchored SNARE syntaxin 17 targets to autophagosomes for fusion with endosomes/lysosomes. Cell 151:1256–1269CrossRefGoogle Scholar
  43. 43.
    Jiang P et al (2014) The HOPS complex mediates autophagosome–lysosome fusion through interaction with syntaxin 17. Mol Biol Cell 25:1327–1337CrossRefGoogle Scholar
  44. 44.
    Yang Z, Klionsky DJ (2010) Mammalian autophagy: core molecular machinery and signaling regulation. Curr Opin Cell Biol 22:124–131CrossRefGoogle Scholar
  45. 45.
    He C, Klionsky DJ (2009) Regulation mechanisms and signaling pathways of autophagy. Annu Rev Genet 43:67–93CrossRefGoogle Scholar
  46. 46.
    Fullgrabe J, Klionsky DJ, Joseph B (2014) The return of the nucleus: transcriptional and epigenetic control of autophagy. Nat Rev Mol Cell Biol 15:65–74CrossRefGoogle Scholar
  47. 47.
    Settembre C et al (2011) TFEB links autophagy to lysosomal biogenesis. Science 332:1429–1433CrossRefGoogle Scholar
  48. 48.
    Chauhan S et al (2013) ZKSCAN3 is a master transcriptional repressor of autophagy. Mol Cell 50:16–28CrossRefGoogle Scholar
  49. 49.
    Li Y et al (2016) Protein kinase C controls lysosome biogenesis independently of mTORC1. Nat Cell Biol 18:1065–1077CrossRefGoogle Scholar
  50. 50.
    Wilkinson S, O’Prey J, Fricker M, Ryan KM (2009) Hypoxia-selective macroautophagy and cell survival signaled by autocrine PDGFR activity. Genes Dev 23:1283–1288CrossRefGoogle Scholar
  51. 51.
    Zhao Y et al (2010) Cytosolic FoxO1 is essential for the induction of autophagy and tumour suppressor activity. Nat Cell Biol 12:665–675CrossRefGoogle Scholar
  52. 52.
    Levine B, Abrams J (2008) p53: The Janus of autophagy? Nat Cell Biol 10:637–639CrossRefGoogle Scholar
  53. 53.
    Copetti T, Bertoli C, Dalla E, Demarchi F, Schneider C (2009) p65/RelA modulates BECN1 transcription and autophagy. Mol Cell Biol 29:2594–2608CrossRefGoogle Scholar
  54. 54.
    Bartholomew CR et al (2012) Ume6 transcription factor is part of a signaling cascade that regulates autophagy. Proc Natl Acad Sci USA 109:11206–11210CrossRefGoogle Scholar
  55. 55.
    Jin M et al (2014) Transcriptional regulation by Pho23 modulates the frequency of autophagosome formation. Curr Biol 24:1314–1322CrossRefGoogle Scholar
  56. 56.
    Bernard A et al (2015) Rph1/KDM4 mediates nutrient-limitation signaling that leads to the transcriptional induction of autophagy. Curr Biol 25:546–555CrossRefGoogle Scholar
  57. 57.
    Decressac M et al (2013) TFEB-mediated autophagy rescues midbrain dopamine neurons from alpha-synuclein toxicity. Proc Natl Acad Sci USA 110:E1817–E1826CrossRefGoogle Scholar
  58. 58.
    Tsunemi T et al (2012) PGC-1alpha rescues Huntington’s disease proteotoxicity by preventing oxidative stress and promoting TFEB function. Sci Transl Med 4:142ra197CrossRefGoogle Scholar
  59. 59.
    Liang XH et al (1999) Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature 402:672–676CrossRefGoogle Scholar
  60. 60.
    Takamura A et al (2011) Autophagy-deficient mice develop multiple liver tumors. Genes Dev 25:795–800CrossRefGoogle Scholar
  61. 61.
    White E (2012) Deconvoluting the context-dependent role for autophagy in cancer. Nat Rev Cancer 12:401–410CrossRefGoogle Scholar
  62. 62.
    Guo JY et al (2013) Autophagy suppresses progression of K-ras-induced lung tumors to oncocytomas and maintains lipid homeostasis. Genes Dev 27:1447–1461CrossRefGoogle Scholar
  63. 63.
    Yang S et al (2011) Pancreatic cancers require autophagy for tumor growth. Genes Dev 25:717–729CrossRefGoogle Scholar
  64. 64.
    De Duve C, Wattiaux R (1966) Functions of lysosomes. Annu Rev Physiol 28:435–492CrossRefGoogle Scholar
  65. 65.
    Rikihisa Y (1984) Glycogen autophagosomes in polymorphonuclear leukocytes induced by rickettsiae. Anat Rec 208:319–327CrossRefGoogle Scholar
  66. 66.
    Nakagawa I et al (2004) Autophagy defends cells against invading group A Streptococcus. Science 306:1037–1040CrossRefGoogle Scholar
  67. 67.
    Gutierrez MG et al (2004) Autophagy is a defense mechanism inhibiting BCG and Mycobacterium tuberculosis survival in infected macrophages. Cell 119:753–766CrossRefGoogle Scholar
  68. 68.
    Birmingham CL, Smith AC, Bakowski MA, Yoshimori T, Brumell JH (2006) Autophagy controls Salmonella infection in response to damage to the Salmonella-containing vacuole. J Biol Chem 281:11374–11383CrossRefGoogle Scholar
  69. 69.
    Ogawa M et al (2005) Escape of intracellular Shigella from autophagy. Science 307:727–731CrossRefGoogle Scholar
  70. 70.
    Levine B, Sodora DL (2006) HIV and CXCR4 in a kiss of autophagic death. J Clin Invest 116:2078–2080CrossRefGoogle Scholar
  71. 71.
    Orvedahl A et al (2010) Autophagy protects against Sindbis virus infection of the central nervous system. Cell Host Microbe 7:115–127CrossRefGoogle Scholar
  72. 72.
    Ling YM et al (2006) Vacuolar and plasma membrane stripping and autophagic elimination of Toxoplasma gondii in primed effector macrophages. J Exp Med 203:2063–2071CrossRefGoogle Scholar
  73. 73.
    Friedrich N, Hagedorn M, Soldati-Favre D, Soldati T (2012) Prison break: pathogens’ strategies to egress from host cells. Microbiol Mol Biol Rev 76:707–720CrossRefGoogle Scholar
  74. 74.
    Rich KA, Burkett C, Webster P (2003) Cytoplasmic bacteria can be targets for autophagy. Cell Microbiol 5:455–468CrossRefGoogle Scholar
  75. 75.
    Cemma M, Kim PK, Brumell JH (2011) The ubiquitin-binding adaptor proteins p62/SQSTM1 and NDP52 are recruited independently to bacteria-associated microdomains to target Salmonella to the autophagy pathway. Autophagy 7:341–345CrossRefGoogle Scholar
  76. 76.
    Mostowy S et al (2010) Entrapment of intracytosolic bacteria by septin cage-like structures. Cell Host Microbe 8:433–444CrossRefGoogle Scholar
  77. 77.
    Ogawa M et al (2011) A Tecpr1-dependent selective autophagy pathway targets bacterial pathogens. Cell Host Microbe 9:376–389CrossRefGoogle Scholar
  78. 78.
    Mesquita FS et al (2012) The Salmonella deubiquitinase SseL inhibits selective autophagy of cytosolic aggregates. PLoS Pathog 8:e1002743CrossRefGoogle Scholar
  79. 79.
    Tattoli I et al (2012) Amino acid starvation induced by invasive bacterial pathogens triggers an innate host defense program. Cell Host Microbe 11:563–575CrossRefGoogle Scholar
  80. 80.
    Hampe J et al (2007) A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1. Nat Genet 39:207–211CrossRefGoogle Scholar
  81. 81.
    Massey DC, Parkes M (2007) Genome-wide association scanning highlights two autophagy genes, ATG16L1 and IRGM, as being significantly associated with Crohn’s disease. Autophagy 3:649–651CrossRefGoogle Scholar
  82. 82.
    Scolaro BL et al (2014) T300A genetic polymorphism: a susceptibility factor for Crohn’s disease? Arq Gastroenterol 51:97–101CrossRefGoogle Scholar
  83. 83.
    Xu Y et al (2007) Toll-like receptor 4 is a sensor for autophagy associated with innate immunity. Immunity 27:135–144CrossRefGoogle Scholar
  84. 84.
    Negroni A et al (2016) NOD2 induces autophagy to control AIEC bacteria infectiveness in intestinal epithelial cells. Inflamm Res 65:803–813CrossRefGoogle Scholar
  85. 85.
    Chauhan S, Mandell MA, Deretic V (2015) IRGM governs the core autophagy machinery to conduct antimicrobial defense. Mol Cell 58:507–521CrossRefGoogle Scholar
  86. 86.
    Visvikis O et al (2014) Innate host defense requires TFEB-mediated transcription of cytoprotective and antimicrobial genes. Immunity 40:896–909CrossRefGoogle Scholar
  87. 87.
    Lee HK et al (2010) In vivo requirement for Atg5 in antigen presentation by dendritic cells. Immunity 32:227–239CrossRefGoogle Scholar
  88. 88.
    Dittmar AJ, Drozda AA, Blader IJ (2016) Drug repurposing screening identifies novel compounds that effectively inhibit toxoplasma gondii growth. mSphere 1:e00042-15CrossRefGoogle Scholar
  89. 89.
    Shu CW, Liu PF, Huang CM (2012) High throughput screening for drug discovery of autophagy modulators. Comb Chem High Throughput Screen 15:721–729CrossRefGoogle Scholar
  90. 90.
    Hipp MS, Park SH, Hartl FU (2014) Proteostasis impairment in protein-misfolding and -aggregation diseases. Trends Cell Biol 24:506–514CrossRefGoogle Scholar
  91. 91.
    Nixon RA (2013) The role of autophagy in neurodegenerative disease. Nat Med 19:983–997CrossRefGoogle Scholar
  92. 92.
    Hara T et al (2006) Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature 441:885–889CrossRefGoogle Scholar
  93. 93.
    Khurana V, Lindquist S (2010) Modelling neurodegeneration in Saccharomyces cerevisiae: why cook with baker’s yeast? Nat Rev Neurosci 11:436–449CrossRefGoogle Scholar
  94. 94.
    Rajasekhar K, Suresh SN, Manjithaya R, Govindaraju T (2015) Rationally designed peptidomimetic modulators of Aβ toxicity in Alzheimer’s disease. Sci Rep 5:8139CrossRefGoogle Scholar
  95. 95.
    Sarkar S et al (2007) Small molecules enhance autophagy and reduce toxicity in Huntington’s disease models. Nat Chem Biol 3:331–338CrossRefGoogle Scholar
  96. 96.
    Subramani S, Malhotra V (2013) Non-autophagic roles of autophagy-related proteins. EMBO Rep 14:143–151CrossRefGoogle Scholar
  97. 97.
    Xie Z, Klionsky DJ (2007) Autophagosome formation: core machinery and adaptations. Nat Cell Biol 9:1102–1109CrossRefGoogle Scholar
  98. 98.
    Mizushima N (2007) Autophagy: process and function. Genes Dev 21:2861–2873CrossRefGoogle Scholar
  99. 99.
    Munz C (2014) Influenza A virus lures autophagic protein LC3 to budding sites. Cell Host Microbe 15:130–131CrossRefGoogle Scholar
  100. 100.
    Beale R et al (2014) A LC3-interacting motif in the influenza A virus M2 protein is required to subvert autophagy and maintain virion stability. Cell Host Microbe 15:239–247CrossRefGoogle Scholar
  101. 101.
    Kimmey JM et al (2015) Unique role for ATG5 in neutrophil-mediated immunopathology during M. tuberculosis infection. Nature 528:565–569CrossRefGoogle Scholar
  102. 102.
    Mauthe M et al (2016) An siRNA screen for ATG protein depletion reveals the extent of the unconventional functions of the autophagy proteome in virus replication. J Cell Biol 214:619–635CrossRefGoogle Scholar
  103. 103.
    Dreux M, Chisari FV (2011) Impact of the autophagy machinery on hepatitis C virus infection. Viruses 3:1342–1357CrossRefGoogle Scholar
  104. 104.
    Hwang S et al (2012) Nondegradative role of Atg5–Atg12/Atg16L1 autophagy protein complex in antiviral activity of interferon gamma. Cell Host Microbe 11:397–409CrossRefGoogle Scholar
  105. 105.
    Martinez J et al (2016) Noncanonical autophagy inhibits the autoinflammatory, lupus-like response to dying cells. Nature 533:115–119CrossRefGoogle Scholar
  106. 106.
    Solvik T, Debnath J (2016) At the crossroads of autophagy and infection: noncanonical roles for ATG proteins in viral replication. J Cell Biol 214:503–505CrossRefGoogle Scholar
  107. 107.
    Zhao Z et al (2007) Coronavirus replication does not require the autophagy gene ATG5. Autophagy 3:581–585CrossRefGoogle Scholar
  108. 108.
    Reggiori F et al (2010) Coronaviruses Hijack the LC3-I-positive EDEMosomes, ER-derived vesicles exporting short-lived ERAD regulators, for replication. Cell Host Microbe 7:500–508CrossRefGoogle Scholar
  109. 109.
    Bell TM, Field EJ, Narang HK (1971) Zika virus infection of the central nervous system of mice. Arch Gesamte Virusforsch 35:183–193CrossRefGoogle Scholar
  110. 110.
    Jheng JR, Ho JY, Horng JT (2014) ER stress, autophagy, and RNA viruses. Front Microbiol 5:388CrossRefGoogle Scholar
  111. 111.
    Hamel R et al (2015) Biology of Zika virus infection in human skin cells. J Virol 89:8880–8896CrossRefGoogle Scholar
  112. 112.
    Harris J et al (2011) Autophagy controls IL-1beta secretion by targeting pro-IL-1β for degradation. J Biol Chem 286:9587–9597CrossRefGoogle Scholar
  113. 113.
    Zhang M, Kenny SJ, Ge L, Xu K, Schekman R (2015) Translocation of interleukin-1β into a vesicle intermediate in autophagy-mediated secretion. Elife 4:e11205Google Scholar
  114. 114.
    Duran JM, Anjard C, Stefan C, Loomis WF, Malhotra V (2010) Unconventional secretion of Acb1 is mediated by autophagosomes. J Cell Biol 188:527–536CrossRefGoogle Scholar
  115. 115.
    Malhotra V (2013) Unconventional protein secretion: an evolving mechanism. EMBO J 32:1660–1664CrossRefGoogle Scholar
  116. 116.
    Manjithaya R, Subramani S (2010) Role of autophagy in unconventional protein secretion. Autophagy 6:650–651CrossRefGoogle Scholar
  117. 117.
    Gee HY, Noh SH, Tang BL, Kim KH, Lee MG (2011) Rescue of ΔF508-CFTR trafficking via a GRASP-dependent unconventional secretion pathway. Cell 146:746–760CrossRefGoogle Scholar
  118. 118.
    DeSelm CJ et al (2011) Autophagy proteins regulate the secretory component of osteoclastic bone resorption. Dev Cell 21:966–974CrossRefGoogle Scholar
  119. 119.
    Ejlerskov P et al (2013) Tubulin polymerization-promoting protein (TPPP/p25α) promotes unconventional secretion of α-synuclein through exophagy by impairing autophagosome–lysosome fusion. J Biol Chem 288:17313–17335CrossRefGoogle Scholar
  120. 120.
    Son SM, Kang S, Choi H, Mook-Jung I (2015) Statins induce insulin-degrading enzyme secretion from astrocytes via an autophagy-based unconventional secretory pathway. Mol Neurodegener 10:56CrossRefGoogle Scholar
  121. 121.
    Son SM et al (2016) Insulin-degrading enzyme secretion from astrocytes is mediated by an autophagy-based unconventional secretory pathway in Alzheimer disease. Autophagy 12:784–800CrossRefGoogle Scholar
  122. 122.
    Nilsson P et al (2013) Abeta secretion and plaque formation depend on autophagy. Cell Rep 5:61–69CrossRefGoogle Scholar
  123. 123.
    Ishibashi K, Uemura T, Waguri S, Fukuda M (2012) Atg16L1, an essential factor for canonical autophagy, participates in hormone secretion from PC12 cells independently of autophagic activity. Mol Biol Cell 23:3193–3202CrossRefGoogle Scholar
  124. 124.
    Cabrera S, Marino G, Fernandez AF, Lopez-Otin C (2010) Autophagy, proteases and the sense of balance. Autophagy 6:961–963CrossRefGoogle Scholar
  125. 125.
    Marino G et al (2010) Autophagy is essential for mouse sense of balance. J Clin Invest 120:2331–2344CrossRefGoogle Scholar
  126. 126.
    Kitamura K et al (2012) Autophagy-related Atg8 localizes to the apicoplast of the human malaria parasite Plasmodium falciparum. PLoS One 7:e42977CrossRefGoogle Scholar
  127. 127.
    Leveque MF et al (2015) Autophagy-related protein ATG8 has a noncanonical function for apicoplast inheritance in Toxoplasma gondii. MBio 6:e01446-15CrossRefGoogle Scholar
  128. 128.
    Thornton GK, Woods CG (2009) Primary microcephaly: do all roads lead to Rome? Trends Genet 25:501–510CrossRefGoogle Scholar
  129. 129.
    Marthiens V et al (2013) Centrosome amplification causes microcephaly. Nat Cell Biol 15:731–740CrossRefGoogle Scholar
  130. 130.
    Simon AK, Clarke AJ (2016) Non-canonical autophagy LAPs lupus. Cell Death Differ 23:1267–1268CrossRefGoogle Scholar
  131. 131.
    Martinez J et al (2015) Molecular characterization of LC3-associated phagocytosis reveals distinct roles for Rubicon, NOX2 and autophagy proteins. Nat Cell Biol 17:893–906CrossRefGoogle Scholar
  132. 132.
    Takeshita F, Kobiyama K, Miyawaki A, Jounai N, Okuda K (2008) The non-canonical role of Atg family members as suppressors of innate antiviral immune signaling. Autophagy 4:67–69CrossRefGoogle Scholar
  133. 133.
    Jounai N et al (2007) The Atg5 Atg12 conjugate associates with innate antiviral immune responses. Proc Natl Acad Sci USA 104:14050–14055CrossRefGoogle Scholar
  134. 134.
    Deretic V (2012) Autophagy: an emerging immunological paradigm. J Immunol 189:15–20CrossRefGoogle Scholar
  135. 135.
    Dupont N et al (2011) Autophagy-based unconventional secretory pathway for extracellular delivery of IL-1β. EMBO J 30:4701–4711CrossRefGoogle Scholar
  136. 136.
    Levine B, Mizushima N, Virgin HW (2011) Autophagy in immunity and inflammation. Nature 469:323–335CrossRefGoogle Scholar
  137. 137.
    Shi CS et al (2012) Activation of autophagy by inflammatory signals limits IL-1beta production by targeting ubiquitinated inflammasomes for destruction. Nat Immunol 13:255–263CrossRefGoogle Scholar
  138. 138.
    Zhou R, Yazdi AS, Menu P, Tschopp J (2011) A role for mitochondria in NLRP3 inflammasome activation. Nature 469:221–225CrossRefGoogle Scholar
  139. 139.
    Xavier RJ, Podolsky DK (2007) Unravelling the pathogenesis of inflammatory bowel disease. Nature 448:427–434CrossRefGoogle Scholar
  140. 140.
    Fujita N et al (2009) Differential involvement of Atg16L1 in Crohn disease and canonical autophagy: analysis of the organization of the Atg16L1 complex in fibroblasts. J Biol Chem 284:32602–32609CrossRefGoogle Scholar
  141. 141.
    Shibata M et al (2010) LC3, a microtubule-associated protein1A/B light chain3, is involved in cytoplasmic lipid droplet formation. Biochem Biophys Res Commun 393:274–279CrossRefGoogle Scholar
  142. 142.
    Velikkakath AK, Nishimura T, Oita E, Ishihara N, Mizushima N (2012) Mammalian Atg2 proteins are essential for autophagosome formation and important for regulation of size and distribution of lipid droplets. Mol Biol Cell 23:896–909CrossRefGoogle Scholar
  143. 143.
    Baerga R, Zhang Y, Chen PH, Goldman S, Jin S (2009) Targeted deletion of autophagy-related 5 (atg5) impairs adipogenesis in a cellular model and in mice. Autophagy 5:1118–1130CrossRefGoogle Scholar
  144. 144.
    Zhang Y et al (2009) Adipose-specific deletion of autophagy-related gene 7 (atg7) in mice reveals a role in adipogenesis. Proc Natl Acad Sci USA 106:19860–19865CrossRefGoogle Scholar
  145. 145.
    Malhotra R, Warne JP, Salas E, Xu AW, Debnath J (2015) Loss of Atg12, but not Atg5, in pro-opiomelanocortin neurons exacerbates diet-induced obesity. Autophagy 11:145–154Google Scholar
  146. 146.
    Ma T et al (2015) Atg5-independent autophagy regulates mitochondrial clearance and is essential for iPSC reprogramming. Nat Cell Biol 17:1379–1387CrossRefGoogle Scholar
  147. 147.
    Tsujimoto Y, Shimizu S (2005) Another way to die: autophagic programmed cell death. Cell Death Differ 12(Suppl 2):1528–1534CrossRefGoogle Scholar
  148. 148.
    Kroemer G, Levine B (2008) Autophagic cell death: the story of a misnomer. Nat Rev Mol Cell Biol 9:1004–1010CrossRefGoogle Scholar

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© Indian Institute of Science 2017

Authors and Affiliations

  • Sarika Chinchwadkar
    • 1
  • Sreedevi Padmanabhan
    • 1
  • Piyush Mishra
    • 1
  • Sunaina Singh
    • 1
  • S. N. Suresh
    • 1
  • Somya Vats
    • 1
  • Gaurav Barve
    • 1
  • Veena Ammanathan
    • 1
  • Ravi Manjithaya
    • 1
    Email author
  1. 1.Autophagy Laboratory, Molecular Biology and Genetics UnitJawaharlal Nehru Centre for Advanced Scientific ResearchBengaluruIndia

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