Skip to main content
SpringerLink
Log in

Multifaceted Housekeeping Functions of Autophagy

  • Review Article
  • Published:
Journal of the Indian Institute of Science Aims and scope

Abstract

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.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1:
Figure 2:

Similar content being viewed by others

References

  1. Mizushima N, Yoshimori T, Ohsumi Y (2011) The role of Atg proteins in autophagosome formation. Annu Rev Cell Dev Biol 27:107–132

    Article  Google Scholar 

  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 119:301–311

    Article  Google Scholar 

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

    Article  Google Scholar 

  4. Kamada Y et al (2000) Tor-mediated induction of autophagy via an Apg1 protein kinase complex. J Cell Biol 150:1507–1513

    Article  Google Scholar 

  5. Suzuki K, Kubota Y, Sekito T, Ohsumi Y (2007) Hierarchy of Atg proteins in pre-autophagosomal structure organization. Genes Cells 12:209–218

    Article  Google Scholar 

  6. Yamamoto H et al (2016) The intrinsically disordered protein Atg13 mediates supramolecular assembly of autophagy initiation complexes. Dev Cell 38:86–99

    Article  Google Scholar 

  7. Ragusa MJ, Stanley RE, Hurley JH (2012) Architecture of the Atg17 complex as a scaffold for autophagosome biogenesis. Cell 151:1501–1512

    Article  Google Scholar 

  8. Reggiori F, Ungermann C (2012) A dimer to bridge early autophagosomal membranes. Cell 151:1403–1405

    Article  Google Scholar 

  9. Rao Y, Perna MG, Hofmann B, Beier V, Wollert T (2016) The Atg1-kinase complex tethers Atg9-vesicles to initiate autophagy. Nat Commun 7:10338

    Article  Google Scholar 

  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 175:925–935

    Article  Google Scholar 

  11. Reggiori F, Shintani T, Nair U, Klionsky DJ (2005) Atg9 cycles between mitochondria and the pre-autophagosomal structure in yeasts. Autophagy 1:101–109

    Article  Google Scholar 

  12. Backues SK et al (2015) Atg23 and Atg27 act at the early stages of Atg9 trafficking in S. cerevisiae. Traffic 16:172–190

    Article  Google Scholar 

  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 6:79–90

    Article  Google Scholar 

  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 283:23972–23980

    Article  Google Scholar 

  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 24:2918–2931

    Article  Google Scholar 

  16. Kirisako T et al (1999) Formation process of autophagosome is traced with Apg8/Aut7p in yeast. J Cell Biol 147:435–446

    Article  Google Scholar 

  17. Reggiori F, Klionsky DJ (2013) Autophagic processes in yeast: mechanism, machinery and regulation. Genetics 194:341–361

    Article  Google Scholar 

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

    Article  Google Scholar 

  19. Yao Z, Delorme-Axford E, Backues SK, Klionsky DJ (2015) Atg41/Icy2 regulates autophagosome formation. Autophagy 11:2288–2299

    Article  Google Scholar 

  20. Cebollero E et al (2012) Phosphatidylinositol-3-phosphate clearance plays a key role in autophagosome completion. Curr Biol 22:1545–1553

    Article  Google Scholar 

  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 14:5258–5270

    Google Scholar 

  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 136:307–317

    Article  Google Scholar 

  23. Haas A, Wickner W (1996) Homotypic vacuole fusion requires Sec17p (yeast alpha-SNAP) and Sec18p (yeast NSF). EMBO J 15:3296–3305

    Google Scholar 

  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 8:2307–2327

    Article  Google Scholar 

  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 97:9402–9407

    Article  Google Scholar 

  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 151:551–562

    Article  Google Scholar 

  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 138:517–529

    Article  Google Scholar 

  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 18:5308–5319

    Article  Google Scholar 

  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 277:47917–47927

    Article  Google Scholar 

  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 183:5942–5955

    Article  Google Scholar 

  31. Teter SA et al (2001) Degradation of lipid vesicles in the yeast vacuole requires function of Cvt17, a putative lipase. J Biol Chem 276:2083–2087

    Article  Google Scholar 

  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 121:338–344

    Article  Google Scholar 

  33. Suriapranata I et al (2000) The breakdown of autophagic vesicles inside the vacuole depends on Aut4p. J Cell Sci 113(Pt 22):4025–4033

    Google Scholar 

  34. Tooze SA, Yoshimori T (2010) The origin of the autophagosomal membrane. Nat Cell Biol 12:831–835

    Article  Google Scholar 

  35. Bento CF et al (2016) Mammalian autophagy: how does it work? Annu Rev Biochem 85:685–713

    Article  Google Scholar 

  36. Yamamoto H et al (2012) Atg9 vesicles are an important membrane source during early steps of autophagosome formation. J Cell Biol 198:219–233

    Article  Google Scholar 

  37. Mizushima N, Yoshimori T, Levine B (2010) Methods in mammalian autophagy research. Cell 140:313–326

    Article  Google Scholar 

  38. Walczak M, Martens S (2013) Dissecting the role of the Atg12–Atg5–Atg16 complex during autophagosome formation. Autophagy 9:424–425

    Article  Google Scholar 

  39. Mizushima N et al (1998) A protein conjugation system essential for autophagy. Nature 395:395–398

    Article  Google Scholar 

  40. Tanida I, Ueno T, Kominami E (2004) LC3 conjugation system in mammalian autophagy. Int J Biochem Cell Biol 36:2503–2518

    Article  Google Scholar 

  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 282:24131–24145

    Article  Google Scholar 

  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 151:1256–1269

    Article  Google Scholar 

  43. Jiang P et al (2014) The HOPS complex mediates autophagosome–lysosome fusion through interaction with syntaxin 17. Mol Biol Cell 25:1327–1337

    Article  Google Scholar 

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

    Article  Google Scholar 

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

    Article  Google Scholar 

  46. Fullgrabe J, Klionsky DJ, Joseph B (2014) The return of the nucleus: transcriptional and epigenetic control of autophagy. Nat Rev Mol Cell Biol 15:65–74

    Article  Google Scholar 

  47. Settembre C et al (2011) TFEB links autophagy to lysosomal biogenesis. Science 332:1429–1433

    Article  Google Scholar 

  48. Chauhan S et al (2013) ZKSCAN3 is a master transcriptional repressor of autophagy. Mol Cell 50:16–28

    Article  Google Scholar 

  49. Li Y et al (2016) Protein kinase C controls lysosome biogenesis independently of mTORC1. Nat Cell Biol 18:1065–1077

    Article  Google Scholar 

  50. Wilkinson S, O’Prey J, Fricker M, Ryan KM (2009) Hypoxia-selective macroautophagy and cell survival signaled by autocrine PDGFR activity. Genes Dev 23:1283–1288

    Article  Google Scholar 

  51. Zhao Y et al (2010) Cytosolic FoxO1 is essential for the induction of autophagy and tumour suppressor activity. Nat Cell Biol 12:665–675

    Article  Google Scholar 

  52. Levine B, Abrams J (2008) p53: The Janus of autophagy? Nat Cell Biol 10:637–639

    Article  Google Scholar 

  53. Copetti T, Bertoli C, Dalla E, Demarchi F, Schneider C (2009) p65/RelA modulates BECN1 transcription and autophagy. Mol Cell Biol 29:2594–2608

    Article  Google Scholar 

  54. Bartholomew CR et al (2012) Ume6 transcription factor is part of a signaling cascade that regulates autophagy. Proc Natl Acad Sci USA 109:11206–11210

    Article  Google Scholar 

  55. Jin M et al (2014) Transcriptional regulation by Pho23 modulates the frequency of autophagosome formation. Curr Biol 24:1314–1322

    Article  Google Scholar 

  56. Bernard A et al (2015) Rph1/KDM4 mediates nutrient-limitation signaling that leads to the transcriptional induction of autophagy. Curr Biol 25:546–555

    Article  Google Scholar 

  57. Decressac M et al (2013) TFEB-mediated autophagy rescues midbrain dopamine neurons from alpha-synuclein toxicity. Proc Natl Acad Sci USA 110:E1817–E1826

    Article  Google Scholar 

  58. Tsunemi T et al (2012) PGC-1alpha rescues Huntington’s disease proteotoxicity by preventing oxidative stress and promoting TFEB function. Sci Transl Med 4:142ra197

    Article  Google Scholar 

  59. Liang XH et al (1999) Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature 402:672–676

    Article  Google Scholar 

  60. Takamura A et al (2011) Autophagy-deficient mice develop multiple liver tumors. Genes Dev 25:795–800

    Article  Google Scholar 

  61. White E (2012) Deconvoluting the context-dependent role for autophagy in cancer. Nat Rev Cancer 12:401–410

    Article  Google Scholar 

  62. Guo JY et al (2013) Autophagy suppresses progression of K-ras-induced lung tumors to oncocytomas and maintains lipid homeostasis. Genes Dev 27:1447–1461

    Article  Google Scholar 

  63. Yang S et al (2011) Pancreatic cancers require autophagy for tumor growth. Genes Dev 25:717–729

    Article  Google Scholar 

  64. De Duve C, Wattiaux R (1966) Functions of lysosomes. Annu Rev Physiol 28:435–492

    Article  Google Scholar 

  65. Rikihisa Y (1984) Glycogen autophagosomes in polymorphonuclear leukocytes induced by rickettsiae. Anat Rec 208:319–327

    Article  Google Scholar 

  66. Nakagawa I et al (2004) Autophagy defends cells against invading group A Streptococcus. Science 306:1037–1040

    Article  Google Scholar 

  67. Gutierrez MG et al (2004) Autophagy is a defense mechanism inhibiting BCG and Mycobacterium tuberculosis survival in infected macrophages. Cell 119:753–766

    Article  Google Scholar 

  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 281:11374–11383

    Article  Google Scholar 

  69. Ogawa M et al (2005) Escape of intracellular Shigella from autophagy. Science 307:727–731

    Article  Google Scholar 

  70. Levine B, Sodora DL (2006) HIV and CXCR4 in a kiss of autophagic death. J Clin Invest 116:2078–2080

    Article  Google Scholar 

  71. Orvedahl A et al (2010) Autophagy protects against Sindbis virus infection of the central nervous system. Cell Host Microbe 7:115–127

    Article  Google Scholar 

  72. Ling YM et al (2006) Vacuolar and plasma membrane stripping and autophagic elimination of Toxoplasma gondii in primed effector macrophages. J Exp Med 203:2063–2071

    Article  Google Scholar 

  73. Friedrich N, Hagedorn M, Soldati-Favre D, Soldati T (2012) Prison break: pathogens’ strategies to egress from host cells. Microbiol Mol Biol Rev 76:707–720

    Article  Google Scholar 

  74. Rich KA, Burkett C, Webster P (2003) Cytoplasmic bacteria can be targets for autophagy. Cell Microbiol 5:455–468

    Article  Google Scholar 

  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 7:341–345

    Article  Google Scholar 

  76. Mostowy S et al (2010) Entrapment of intracytosolic bacteria by septin cage-like structures. Cell Host Microbe 8:433–444

    Article  Google Scholar 

  77. Ogawa M et al (2011) A Tecpr1-dependent selective autophagy pathway targets bacterial pathogens. Cell Host Microbe 9:376–389

    Article  Google Scholar 

  78. Mesquita FS et al (2012) The Salmonella deubiquitinase SseL inhibits selective autophagy of cytosolic aggregates. PLoS Pathog 8:e1002743

    Article  Google Scholar 

  79. Tattoli I et al (2012) Amino acid starvation induced by invasive bacterial pathogens triggers an innate host defense program. Cell Host Microbe 11:563–575

    Article  Google Scholar 

  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 39:207–211

    Article  Google Scholar 

  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 3:649–651

    Article  Google Scholar 

  82. Scolaro BL et al (2014) T300A genetic polymorphism: a susceptibility factor for Crohn’s disease? Arq Gastroenterol 51:97–101

    Article  Google Scholar 

  83. Xu Y et al (2007) Toll-like receptor 4 is a sensor for autophagy associated with innate immunity. Immunity 27:135–144

    Article  Google Scholar 

  84. Negroni A et al (2016) NOD2 induces autophagy to control AIEC bacteria infectiveness in intestinal epithelial cells. Inflamm Res 65:803–813

    Article  Google Scholar 

  85. Chauhan S, Mandell MA, Deretic V (2015) IRGM governs the core autophagy machinery to conduct antimicrobial defense. Mol Cell 58:507–521

    Article  Google Scholar 

  86. Visvikis O et al (2014) Innate host defense requires TFEB-mediated transcription of cytoprotective and antimicrobial genes. Immunity 40:896–909

    Article  Google Scholar 

  87. Lee HK et al (2010) In vivo requirement for Atg5 in antigen presentation by dendritic cells. Immunity 32:227–239

    Article  Google Scholar 

  88. Dittmar AJ, Drozda AA, Blader IJ (2016) Drug repurposing screening identifies novel compounds that effectively inhibit toxoplasma gondii growth. mSphere 1:e00042-15

    Article  Google Scholar 

  89. Shu CW, Liu PF, Huang CM (2012) High throughput screening for drug discovery of autophagy modulators. Comb Chem High Throughput Screen 15:721–729

    Article  Google Scholar 

  90. Hipp MS, Park SH, Hartl FU (2014) Proteostasis impairment in protein-misfolding and -aggregation diseases. Trends Cell Biol 24:506–514

    Article  Google Scholar 

  91. Nixon RA (2013) The role of autophagy in neurodegenerative disease. Nat Med 19:983–997

    Article  Google Scholar 

  92. Hara T et al (2006) Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature 441:885–889

    Article  Google Scholar 

  93. Khurana V, Lindquist S (2010) Modelling neurodegeneration in Saccharomyces cerevisiae: why cook with baker’s yeast? Nat Rev Neurosci 11:436–449

    Article  Google Scholar 

  94. Rajasekhar K, Suresh SN, Manjithaya R, Govindaraju T (2015) Rationally designed peptidomimetic modulators of Aβ toxicity in Alzheimer’s disease. Sci Rep 5:8139

    Article  Google Scholar 

  95. Sarkar S et al (2007) Small molecules enhance autophagy and reduce toxicity in Huntington’s disease models. Nat Chem Biol 3:331–338

    Article  Google Scholar 

  96. Subramani S, Malhotra V (2013) Non-autophagic roles of autophagy-related proteins. EMBO Rep 14:143–151

    Article  Google Scholar 

  97. Xie Z, Klionsky DJ (2007) Autophagosome formation: core machinery and adaptations. Nat Cell Biol 9:1102–1109

    Article  Google Scholar 

  98. Mizushima N (2007) Autophagy: process and function. Genes Dev 21:2861–2873

    Article  Google Scholar 

  99. Munz C (2014) Influenza A virus lures autophagic protein LC3 to budding sites. Cell Host Microbe 15:130–131

    Article  Google Scholar 

  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 15:239–247

    Article  Google Scholar 

  101. Kimmey JM et al (2015) Unique role for ATG5 in neutrophil-mediated immunopathology during M. tuberculosis infection. Nature 528:565–569

    Article  Google Scholar 

  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 214:619–635

    Article  Google Scholar 

  103. Dreux M, Chisari FV (2011) Impact of the autophagy machinery on hepatitis C virus infection. Viruses 3:1342–1357

    Article  Google Scholar 

  104. Hwang S et al (2012) Nondegradative role of Atg5–Atg12/Atg16L1 autophagy protein complex in antiviral activity of interferon gamma. Cell Host Microbe 11:397–409

    Article  Google Scholar 

  105. Martinez J et al (2016) Noncanonical autophagy inhibits the autoinflammatory, lupus-like response to dying cells. Nature 533:115–119

    Article  Google Scholar 

  106. Solvik T, Debnath J (2016) At the crossroads of autophagy and infection: noncanonical roles for ATG proteins in viral replication. J Cell Biol 214:503–505

    Article  Google Scholar 

  107. Zhao Z et al (2007) Coronavirus replication does not require the autophagy gene ATG5. Autophagy 3:581–585

    Article  Google Scholar 

  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 7:500–508

    Article  Google Scholar 

  109. Bell TM, Field EJ, Narang HK (1971) Zika virus infection of the central nervous system of mice. Arch Gesamte Virusforsch 35:183–193

    Article  Google Scholar 

  110. Jheng JR, Ho JY, Horng JT (2014) ER stress, autophagy, and RNA viruses. Front Microbiol 5:388

    Article  Google Scholar 

  111. Hamel R et al (2015) Biology of Zika virus infection in human skin cells. J Virol 89:8880–8896

    Article  Google Scholar 

  112. Harris J et al (2011) Autophagy controls IL-1beta secretion by targeting pro-IL-1β for degradation. J Biol Chem 286:9587–9597

    Article  Google Scholar 

  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:e11205

    Google Scholar 

  114. Duran JM, Anjard C, Stefan C, Loomis WF, Malhotra V (2010) Unconventional secretion of Acb1 is mediated by autophagosomes. J Cell Biol 188:527–536

    Article  Google Scholar 

  115. Malhotra V (2013) Unconventional protein secretion: an evolving mechanism. EMBO J 32:1660–1664

    Article  Google Scholar 

  116. Manjithaya R, Subramani S (2010) Role of autophagy in unconventional protein secretion. Autophagy 6:650–651

    Article  Google Scholar 

  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 146:746–760

    Article  Google Scholar 

  118. DeSelm CJ et al (2011) Autophagy proteins regulate the secretory component of osteoclastic bone resorption. Dev Cell 21:966–974

    Article  Google Scholar 

  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 288:17313–17335

    Article  Google Scholar 

  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 10:56

    Article  Google Scholar 

  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 12:784–800

    Article  Google Scholar 

  122. Nilsson P et al (2013) Abeta secretion and plaque formation depend on autophagy. Cell Rep 5:61–69

    Article  Google Scholar 

  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 23:3193–3202

    Article  Google Scholar 

  124. Cabrera S, Marino G, Fernandez AF, Lopez-Otin C (2010) Autophagy, proteases and the sense of balance. Autophagy 6:961–963

    Article  Google Scholar 

  125. Marino G et al (2010) Autophagy is essential for mouse sense of balance. J Clin Invest 120:2331–2344

    Article  Google Scholar 

  126. Kitamura K et al (2012) Autophagy-related Atg8 localizes to the apicoplast of the human malaria parasite Plasmodium falciparum. PLoS One 7:e42977

    Article  Google Scholar 

  127. Leveque MF et al (2015) Autophagy-related protein ATG8 has a noncanonical function for apicoplast inheritance in Toxoplasma gondii. MBio 6:e01446-15

    Article  Google Scholar 

  128. Thornton GK, Woods CG (2009) Primary microcephaly: do all roads lead to Rome? Trends Genet 25:501–510

    Article  Google Scholar 

  129. Marthiens V et al (2013) Centrosome amplification causes microcephaly. Nat Cell Biol 15:731–740

    Article  Google Scholar 

  130. Simon AK, Clarke AJ (2016) Non-canonical autophagy LAPs lupus. Cell Death Differ 23:1267–1268

    Article  Google Scholar 

  131. Martinez J et al (2015) Molecular characterization of LC3-associated phagocytosis reveals distinct roles for Rubicon, NOX2 and autophagy proteins. Nat Cell Biol 17:893–906

    Article  Google Scholar 

  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 4:67–69

    Article  Google Scholar 

  133. Jounai N et al (2007) The Atg5 Atg12 conjugate associates with innate antiviral immune responses. Proc Natl Acad Sci USA 104:14050–14055

    Article  Google Scholar 

  134. Deretic V (2012) Autophagy: an emerging immunological paradigm. J Immunol 189:15–20

    Article  Google Scholar 

  135. Dupont N et al (2011) Autophagy-based unconventional secretory pathway for extracellular delivery of IL-1β. EMBO J 30:4701–4711

    Article  Google Scholar 

  136. Levine B, Mizushima N, Virgin HW (2011) Autophagy in immunity and inflammation. Nature 469:323–335

    Article  Google Scholar 

  137. Shi CS et al (2012) Activation of autophagy by inflammatory signals limits IL-1beta production by targeting ubiquitinated inflammasomes for destruction. Nat Immunol 13:255–263

    Article  Google Scholar 

  138. Zhou R, Yazdi AS, Menu P, Tschopp J (2011) A role for mitochondria in NLRP3 inflammasome activation. Nature 469:221–225

    Article  Google Scholar 

  139. Xavier RJ, Podolsky DK (2007) Unravelling the pathogenesis of inflammatory bowel disease. Nature 448:427–434

    Article  Google Scholar 

  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 284:32602–32609

    Article  Google Scholar 

  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 393:274–279

    Article  Google Scholar 

  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 23:896–909

    Article  Google Scholar 

  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 5:1118–1130

    Article  Google Scholar 

  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 106:19860–19865

    Article  Google Scholar 

  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 11:145–154

    Google Scholar 

  146. Ma T et al (2015) Atg5-independent autophagy regulates mitochondrial clearance and is essential for iPSC reprogramming. Nat Cell Biol 17:1379–1387

    Article  Google Scholar 

  147. Tsujimoto Y, Shimizu S (2005) Another way to die: autophagic programmed cell death. Cell Death Differ 12(Suppl 2):1528–1534

    Article  Google Scholar 

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

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Autophagy Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bengaluru, 560 064, India

    Sarika Chinchwadkar, Sreedevi Padmanabhan, Piyush Mishra, Sunaina Singh, S. N. Suresh, Somya Vats, Gaurav Barve, Veena Ammanathan & Ravi Manjithaya

Authors
  1. Sarika Chinchwadkar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sreedevi Padmanabhan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Piyush Mishra
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sunaina Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S. N. Suresh
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Somya Vats
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Gaurav Barve
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Veena Ammanathan
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ravi Manjithaya
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ravi Manjithaya.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chinchwadkar, S., Padmanabhan, S., Mishra, P. et al. Multifaceted Housekeeping Functions of Autophagy. J Indian Inst Sci 97, 79–94 (2017). https://doi.org/10.1007/s41745-016-0015-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s41745-016-0015-z

Keywords

Search

Navigation