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Abstract

Macroautophagy is an intracellular degradation system that delivers diverse cytoplasmic materials to lysosomes via autophagosomes. Recent advances have enabled identification of several selective autophagy substrates and receptors, greatly expanding our understanding of the cellular functions of autophagy. In this review, we describe the diverse cellular functions of macroautophagy, including its essential contribution to metabolic adaptation and cellular homeostasis. We also discuss emerging findings on the mechanisms and functions of various types of selective autophagy.

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2019-10-06
2024-04-23
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Literature Cited

  1. Al Rawi S, Louvet-Vallee S, Djeddi A, Sachse M, Culetto E et al. 2011. Postfertilization autophagy of sperm organelles prevents paternal mitochondrial DNA transmission. Science 334:1144–47
    [Google Scholar]
  2. Allen GF, Toth R, James J, Ganley IG 2013. Loss of iron triggers PINK1/Parkin-independent mitophagy. EMBO Rep 14:1127–35
    [Google Scholar]
  3. Amaravadi R, Kimmelman AC, White E 2016. Recent insights into the function of autophagy in cancer. Genes Dev 30:1913–30
    [Google Scholar]
  4. An H, Ordureau A, Paulo JA, Shoemaker CJ, Denic V, Harper JW 2019. TEX264 is an endoplasmic reticulum-resident ATG8-interacting protein critical for ER remodeling during nutrient stress. Mol. Cell 74:891–908.e10
    [Google Scholar]
  5. Arosio P, Ingrassia R, Cavadini P 2009. Ferritins: a family of molecules for iron storage, antioxidation and more. Biochim. Biophys. Acta 1790:589–99
    [Google Scholar]
  6. Asano T, Komatsu M, Yamaguchi-Iwai Y, Ishikawa F, Mizushima N, Iwai K 2011. Distinct mechanisms of ferritin delivery to lysosomes in iron-depleted and iron-replete cells. Mol. Cell. Biol. 31:2040–52
    [Google Scholar]
  7. Axe EL, Walker SA, Manifava M, Chandra P, Roderick HL et al. 2008. Autophagosome formation from membrane compartments enriched in phosphatidylinositol 3-phosphate and dynamically connected to the endoplasmic reticulum. J. Cell Biol. 182:685–701
    [Google Scholar]
  8. Bas L, Papinski D, Kraft C 2018. Ykt6 mediates autophagosome-vacuole fusion. Mol. Cell. Oncol. 5:e1526006
    [Google Scholar]
  9. Bellelli R, Federico G, Matte A, Colecchia D, Iolascon A et al. 2016. NCOA4 deficiency impairs systemic iron homeostasis. Cell Rep 14:411–21
    [Google Scholar]
  10. Bhujabal Z, Birgisdottir AB, Sjottem E, Brenne HB, Overvatn A et al. 2017. FKBP8 recruits LC3A to mediate Parkin-independent mitophagy. EMBO Rep 18:947–61
    [Google Scholar]
  11. Bjorkoy G, Lamark T, Brech A, Outzen H, Perander M et al. 2005. p62/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death. J. Cell Biol. 171:603–14
    [Google Scholar]
  12. Buchan JR, Kolaitis RM, Taylor JP, Parker R 2013. Eukaryotic stress granules are cleared by autophagy and Cdc48/VCP function. Cell 153:1461–74
    [Google Scholar]
  13. Cadwell K, Debnath J. 2018. Beyond self-eating: the control of nonautophagic functions and signaling pathways by autophagy-related proteins. J. Cell Biol. 217:813–22
    [Google Scholar]
  14. Chan NC, Salazar AM, Pham AH, Sweredoski MJ, Kolawa NJ et al. 2011. Broad activation of the ubiquitin-proteasome system by Parkin is critical for mitophagy. Hum. Mol. Genet. 20:1726–37
    [Google Scholar]
  15. Chauhan S, Kumar S, Jain A, Ponpuak M, Mudd MH et al. 2016. TRIMs and galectins globally cooperate and TRIM16 and galectin-3 co-direct autophagy in endomembrane damage homeostasis. Dev. Cell 39:13–27
    [Google Scholar]
  16. Chen Q, Xiao Y, Chai P, Zheng P, Teng J et al. 2019. ATL3 is a tubular ER-phagy receptor for GABARAP-mediated selective autophagy. Curr. Biol. 29:846–55
    [Google Scholar]
  17. Chino H, Hatta T, Natsume T, Mizushima N 2019. Intrinsically disordered protein TEX264 mediates ER-phagy. Mol. Cell 74:909–21.e6
    [Google Scholar]
  18. Chu CT, Ji J, Dagda RK, Jiang JF, Tyurina YY et al. 2013. Cardiolipin externalization to the outer mitochondrial membrane acts as an elimination signal for mitophagy in neuronal cells. Nat. Cell Biol. 15:1197–205
    [Google Scholar]
  19. Cohen-Kaplan V, Livneh I, Avni N, Fabre B, Ziv T et al. 2016. p62- and ubiquitin-dependent stress-induced autophagy of the mammalian 26S proteasome. PNAS 113:E7490–99
    [Google Scholar]
  20. Dengjel J, Hoyer-Hansen M, Nielsen MO, Eisenberg T, Harder LM et al. 2012. Identification of autophagosome-associated proteins and regulators by quantitative proteomic analysis and genetic screens. Mol. Cell. Proteom. 11:M111.014035
    [Google Scholar]
  21. Deosaran E, Larsen KB, Hua R, Sargent G, Wang Y et al. 2013. NBR1 acts as an autophagy receptor for peroxisomes. J. Cell Sci. 126:939–52
    [Google Scholar]
  22. Deretic V, Saitoh T, Akira S 2013. Autophagy in infection, inflammation and immunity. Nat. Rev. Immunol. 13:722–37
    [Google Scholar]
  23. Dooley HC, Razi M, Polson HE, Girardin SE, Wilson MI, Tooze SA 2014. WIPI2 links LC3 conjugation with PI3P, autophagosome formation, and pathogen clearance by recruiting Atg12-5-16L1. Mol. Cell 55:238–52
    [Google Scholar]
  24. Dowdle WE, Nyfeler B, Nagel J, Elling RA, Liu S et al. 2014. Selective VPS34 inhibitor blocks autophagy and uncovers a role for NCOA4 in ferritin degradation and iron homeostasis in vivo. Nat. Cell Biol. 16:1069–79
    [Google Scholar]
  25. Ezaki J, Matsumoto N, Takeda-Ezaki M, Komatsu M, Takahashi K et al. 2011. Liver autophagy contributes to the maintenance of blood glucose and amino acid levels. Autophagy 7:727–36
    [Google Scholar]
  26. Farré J-C, Manjithaya R, Mathewson RD, Subramani S 2008. PpAtg30 tags peroxisomes for turnover by selective autophagy. Dev. Cell 14:365–76
    [Google Scholar]
  27. Farré J-C, Subramani S. 2016. Mechanistic insights into selective autophagy pathways: lessons from yeast. Nat. Rev. Mol. Cell Biol. 17:537–52
    [Google Scholar]
  28. Frankel LB, Lubas M, Lund AH 2017. Emerging connections between RNA and autophagy. Autophagy 13:3–23
    [Google Scholar]
  29. Fujita N, Morita E, Itoh T, Tanaka A, Nakaoka M et al. 2013. Recruitment of the autophagic machinery to endosomes during infection is mediated by ubiquitin. J. Cell Biol. 203:115–28
    [Google Scholar]
  30. Fumagalli F, Noack J, Bergmann TJ, Cebollero E, Pisoni GB et al. 2016. Translocon component Sec62 acts in endoplasmic reticulum turnover during stress recovery. Nat. Cell Biol. 18:1173–84
    [Google Scholar]
  31. Galluzzi L, Baehrecke EH, Ballabio A, Boya P, Bravo-San Pedro JM et al. 2017. Molecular definitions of autophagy and related processes. EMBO J 36:1811–36
    [Google Scholar]
  32. Gatica D, Lahiri V, Klionsky DJ 2018. Cargo recognition and degradation by selective autophagy. Nat. Cell Biol. 20:233–42
    [Google Scholar]
  33. Goodwin JM, Dowdle WE, DeJesus R, Wang Z, Bergman P et al. 2017. Autophagy-independent lysosomal targeting regulated by ULK1/2-FIP200 and ATG9. Cell Rep 20:2341–56
    [Google Scholar]
  34. Grumati P, Morozzi G, Holper S, Mari M, Harwardt MI et al. 2017. Full length RTN3 regulates turnover of tubular endoplasmic reticulum via selective autophagy. eLife 6:e25555
    [Google Scholar]
  35. Guo JY, Teng X, Laddha SV, Ma S, Van Nostrand SC et al. 2016. Autophagy provides metabolic substrates to maintain energy charge and nucleotide pools in Ras-driven lung cancer cells. Genes Dev 30:1704–17
    [Google Scholar]
  36. Hanna RA, Quinsay MN, Orogo AM, Giang K, Rikka S, Gustafsson AB 2012. Microtubule-associated protein 1 light chain 3 (LC3) interacts with Bnip3 protein to selectively remove endoplasmic reticulum and mitochondria via autophagy. J. Biol. Chem. 287:19094–104
    [Google Scholar]
  37. Hansen M, Rubinsztein DC, Walker DW 2018. Autophagy as a promoter of longevity: insights from model organisms. Nat. Rev. Mol. Cell Biol. 19:579–93
    [Google Scholar]
  38. Hara T, Nakamura K, Matsui M, Yamamoto A, Nakahara Y et al. 2006. Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature 441:885–89
    [Google Scholar]
  39. Herhaus L, Dikic I. 2018. Regulation of Salmonella-host cell interactions via the ubiquitin system. Int. J. Med. Microbiol. 308:176–84
    [Google Scholar]
  40. Huang H, Kawamata T, Horie T, Tsugawa H, Nakayama Y et al. 2015. Bulk RNA degradation by nitrogen starvation–induced autophagy in yeast. EMBO J 34:154–68
    [Google Scholar]
  41. Hung YH, Chen LM, Yang JY, Yang WY 2013. Spatiotemporally controlled induction of autophagy-mediated lysosome turnover. Nat. Commun. 4:2111
    [Google Scholar]
  42. Ichimura Y, Waguri S, Sou YS, Kageyama S, Hasegawa J et al. 2013. Phosphorylation of p62 activates the Keap1-Nrf2 pathway during selective autophagy. Mol. Cell 51:618–31
    [Google Scholar]
  43. Iershov A, Nemazanyy I, Alkhoury C, Girard M, Barth E et al. 2019. The class 3 PI3K coordinates autophagy and mitochondrial lipid catabolism by controlling nuclear receptor PPARα. Nat. Commun. 10:1566
    [Google Scholar]
  44. Itakura E, Kishi-Itakura C, Koyama-Honda I, Mizushima N 2012. Structures containing Atg9A and the ULK1 complex independently target depolarized mitochondria at initial stages of Parkin-mediated mitophagy. J. Cell Sci. 125:1488–99
    [Google Scholar]
  45. Jiang S, Heller B, Tagliabracci VS, Zhai L, Irimia JM et al. 2010. Starch binding domain–containing protein 1/genethonin 1 is a novel participant in glycogen metabolism. J. Biol. Chem. 285:34960–71
    [Google Scholar]
  46. Kabeya Y, Mizushima N, Ueno T, Yamamoto A, Kirisako T et al. 2000. LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J 19:5720–28
    [Google Scholar]
  47. Kaizuka T, Morishita H, Hama Y, Tsukamoto S, Matsui T et al. 2016. An autophagic flux probe that releases an internal control. Mol. Cell 64:835–49
    [Google Scholar]
  48. Kane LA, Lazarou M, Fogel AI, Li Y, Yamano K et al. 2014. PINK1 phosphorylates ubiquitin to activate Parkin E3 ubiquitin ligase activity. J. Cell Biol. 205:143–53
    [Google Scholar]
  49. Kanki T, Wang K, Cao Y, Baba M, Klionsky DJ 2009. Atg32 is a mitochondrial protein that confers selectivity during mitophagy. Dev. Cell 17:98–109
    [Google Scholar]
  50. Karanasios E, Walker SA, Okkenhaug H, Manifava M, Hummel E et al. 2016. Autophagy initiation by ULK complex assembly on ER tubulovesicular regions marked by ATG9 vesicles. Nat. Commun. 7:12420
    [Google Scholar]
  51. Karsli-Uzunbas G, Guo JY, Price S, Teng X, Laddha SV et al. 2014. Autophagy is required for glucose homeostasis and lung tumor maintenance. Cancer Discov 4:914–27
    [Google Scholar]
  52. Katayama H, Kogure T, Mizushima N, Yoshimori T, Miyawaki A 2011. A sensitive and quantitative technique for detecting autophagic events based on lysosomal delivery. Chem. Biol. 18:1042–52
    [Google Scholar]
  53. Katheder NS, Khezri R, O'Farrell F, Schultz SW, Jain A et al. 2017. Microenvironmental autophagy promotes tumour growth. Nature 541:417–20
    [Google Scholar]
  54. Kaur J, Debnath J. 2015. Autophagy at the crossroads of catabolism and anabolism. Nat. Rev. Mol. Cell Biol. 16:461–72
    [Google Scholar]
  55. Kaushik S, Cuervo AM. 2018. The coming of age of chaperone-mediated autophagy. Nat. Rev. Mol. Cell Biol. 19:365–81
    [Google Scholar]
  56. Kawamata T, Horie T, Matsunami M, Sasaki M, Ohsumi Y 2017. Zinc starvation induces autophagy in yeast. J. Biol. Chem. 292:8520–30
    [Google Scholar]
  57. Kazlauskaite A, Kondapalli C, Gourlay R, Campbell DG, Ritorto MS et al. 2014. Parkin is activated by PINK1-dependent phosphorylation of ubiquitin at Ser65. Biochem. J. 460:127–39
    [Google Scholar]
  58. Khaminets A, Behl C, Dikic I 2016. Ubiquitin-dependent and independent signals in selective autophagy. Trends Cell Biol 26:6–16
    [Google Scholar]
  59. Khaminets A, Heinrich T, Mari M, Grumati P, Huebner AK et al. 2015. Regulation of endoplasmic reticulum turnover by selective autophagy. Nature 522:354–58
    [Google Scholar]
  60. Kim PK, Hailey DW, Mullen RT, Lippincott-Schwartz J 2008. Ubiquitin signals autophagic degradation of cytosolic proteins and peroxisomes. PNAS 105:20567–74
    [Google Scholar]
  61. Kimura S, Noda T, Yoshimori T 2007. Dissection of the autophagosome maturation process by a novel reporter protein, tandem fluorescent-tagged LC3. Autophagy 3:452–60
    [Google Scholar]
  62. Kirkin V, Lamark T, Sou YS, Bjorkoy G, Nunn JL et al. 2009. A role for NBR1 in autophagosomal degradation of ubiquitinated substrates. Mol. Cell 33:505–16
    [Google Scholar]
  63. Kishi-Itakura C, Koyama-Honda I, Itakura E, Mizushima N 2014. Ultrastructural analysis of autophagosome organization using mammalian autophagy-deficient cells. J. Cell Sci. 127:4089–102
    [Google Scholar]
  64. Klionsky DJ, Abdelmohsen K, Abe A, Abedin MJ, Abeliovich H et al. 2016. Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy 12:1–222 Erratum. 2016. Autophagy 12:443
    [Google Scholar]
  65. Klionsky DJ, Cregg JM, Dunn WA Jr, Emr SD, Sakai Y et al. 2003. A unified nomenclature for yeast autophagy-related genes. Dev. Cell 5:539–45
    [Google Scholar]
  66. Komatsu M, Waguri S, Chiba T, Murata S, Iwata J et al. 2006. Loss of autophagy in the central nervous system causes neurodegeneration in mice. Nature 441:880–84
    [Google Scholar]
  67. Komatsu M, Waguri S, Koike M, Sou YS, Ueno T et al. 2007. Homeostatic levels of p62 control cytoplasmic inclusion body formation in autophagy-deficient mice. Cell 131:1149–63
    [Google Scholar]
  68. Komatsu M, Waguri S, Ueno T, Iwata J, Murata S et al. 2005. Impairment of starvation-induced and constitutive autophagy in Atg7-deficient mice. J. Cell Biol. 169:425–34
    [Google Scholar]
  69. Korac J, Schaeffer V, Kovacevic I, Clement AM, Jungblut B et al. 2013. Ubiquitin-independent function of optineurin in autophagic clearance of protein aggregates. J. Cell Sci. 126:580–92
    [Google Scholar]
  70. Koyano F, Okatsu K, Kosako H, Tamura Y, Go E et al. 2014. Ubiquitin is phosphorylated by PINK1 to activate parkin. Nature 510:162–66
    [Google Scholar]
  71. Kraft C, Deplazes A, Sohrmann M, Peter M 2008. Mature ribosomes are selectively degraded upon starvation by an autophagy pathway requiring the Ubp3p/Bre5p ubiquitin protease. Nat. Cell Biol. 10:602–10
    [Google Scholar]
  72. Kroemer G. 2015. Autophagy: a druggable process that is deregulated in aging and human disease. J. Clin. Investig. 125:1–4
    [Google Scholar]
  73. Kuma A, Hatano M, Matsui M, Yamamoto A, Nakaya H et al. 2004. The role of autophagy during the early neonatal starvation period. Nature 432:1032–36
    [Google Scholar]
  74. Kuma A, Komatsu M, Mizushima N 2017. Autophagy-monitoring and autophagy-deficient mice. Autophagy 13:1619–28
    [Google Scholar]
  75. Lazarou M, Sliter DA, Kane LA, Sarraf SA, Wang C et al. 2015. The ubiquitin kinase PINK1 recruits autophagy receptors to induce mitophagy. Nature 524:309–14
    [Google Scholar]
  76. Lee JJ, Sanchez-Martinez A, Zarate AM, Beninca C, Mayor U et al. 2018. Basal mitophagy is widespread in Drosophila but minimally affected by loss of Pink1 or parkin. J. Cell Biol. 217:1613–22
    [Google Scholar]
  77. Leidal AM, Levine B, Debnath J 2018. Autophagy and the cell biology of age-related disease. Nat. Cell Biol. 20:1338–48
    [Google Scholar]
  78. Levine B, Packer M, Codogno P 2015. Development of autophagy inducers in clinical medicine. J. Clin. Investig. 125:14–24
    [Google Scholar]
  79. Liu L, Feng D, Chen G, Chen M, Zheng Q et al. 2012. Mitochondrial outer-membrane protein FUNDC1 mediates hypoxia-induced mitophagy in mammalian cells. Nat. Cell Biol. 14:177–85
    [Google Scholar]
  80. Liu Y, Zou W, Yang P, Wang L, Ma Y et al. 2018. Autophagy-dependent ribosomal RNA degradation is essential for maintaining nucleotide homeostasis during C. elegans development. eLife 7:e36588
    [Google Scholar]
  81. Lu K, Psakhye I, Jentsch S 2014. Autophagic clearance of polyQ proteins mediated by ubiquitin-Atg8 adaptors of the conserved CUET protein family. Cell 158:549–63
    [Google Scholar]
  82. Ma D, Molusky MM, Song J, Hu CR, Fang F et al. 2013. Autophagy deficiency by hepatic FIP200 deletion uncouples steatosis from liver injury in NAFLD. Mol. Endocrinol. 27:1643–54
    [Google Scholar]
  83. Maejima I, Takahashi A, Omori H, Kimura T, Takabatake Y et al. 2013. Autophagy sequesters damaged lysosomes to control lysosomal biogenesis and kidney injury. EMBO J 32:2336–47
    [Google Scholar]
  84. Mancias JD, Pontano Vaites L, Nissim S, Biancur DE, Kim AJ et al. 2015. Ferritinophagy via NCOA4 is required for erythropoiesis and is regulated by iron dependent HERC2-mediated proteolysis. eLife 4:e10308
    [Google Scholar]
  85. Mancias JD, Wang X, Gygi SP, Harper JW, Kimmelman AC 2014. Quantitative proteomics identifies NCOA4 as the cargo receptor mediating ferritinophagy. Nature 509:105–9
    [Google Scholar]
  86. Mandell MA, Jain A, Arko-Mensah J, Chauhan S, Kimura T et al. 2014. TRIM proteins regulate autophagy and can target autophagic substrates by direct recognition. Dev. Cell 30:394–409
    [Google Scholar]
  87. Marshall RS, Li F, Gemperline DC, Book AJ, Vierstra RD 2015. Autophagic degradation of the 26S proteasome is mediated by the dual ATG8/ubiquitin receptor RPN10 in Arabidopsis. Mol. Cell 58:1053–66
    [Google Scholar]
  88. Marshall RS, McLoughlin F, Vierstra RD 2016. Autophagic turnover of inactive 26S proteasomes in yeast is directed by the ubiquitin receptor Cue5 and the Hsp42 chaperone. Cell Rep 16:1717–32
    [Google Scholar]
  89. Martinez-Lopez N, Singh R. 2015. Autophagy and lipid droplets in the liver. Annu. Rev. Nutr. 35:215–37
    [Google Scholar]
  90. Matsui M, Yamamoto A, Kuma A, Ohsumi Y, Mizushima N 2006. Organelle degradation during the lens and erythroid differentiation is independent of autophagy. Biochem. Biophys. Res. Commun. 339:485–89
    [Google Scholar]
  91. McWilliams TG, Prescott AR, Montava-Garriga L, Ball G, Singh F et al. 2018. Basal mitophagy occurs independently of PINK1 in mouse tissues of high metabolic demand. Cell Metab 27:439–49.e5
    [Google Scholar]
  92. Mejlvang J, Olsvik H, Svenning S, Bruun JA, Abudu YP et al. 2018. Starvation induces rapid degradation of selective autophagy receptors by endosomal microautophagy. J. Cell Biol. 217:3640–55
    [Google Scholar]
  93. Mizushima N. 2018. A brief history of autophagy from cell biology to physiology and disease. Nat. Cell Biol. 20:521–27
    [Google Scholar]
  94. Mizushima N, Komatsu M. 2011. Autophagy: renovation of cells and tissues. Cell 147:728–41
    [Google Scholar]
  95. Mizushima N, Yamamoto A, Matsui M, Yoshimori T, Ohsumi Y 2004. In vivo analysis of autophagy in response to nutrient starvation using transgenic mice expressing a fluorescent autophagosome marker. Mol. Biol. Cell 15:1101–11
    [Google Scholar]
  96. Mizushima N, Yoshimori T, Levine B 2010. Methods in mammalian autophagy research. Cell 140:313–26
    [Google Scholar]
  97. Mizushima N, Yoshimori T, Ohsumi Y 2011. The role of Atg proteins in autophagosome formation. Annu. Rev. Cell Dev. Biol. 27:107–32
    [Google Scholar]
  98. Mochida K, Oikawa Y, Kimura Y, Kirisako H, Hirano H et al. 2015. Receptor-mediated selective autophagy degrades the endoplasmic reticulum and the nucleus. Nature 522:359–62
    [Google Scholar]
  99. Moretti F, Bergman P, Dodgson S, Marcellin D, Claerr I et al. 2018. TMEM41B is a novel regulator of autophagy and lipid mobilization. EMBO Rep 19:e45889
    [Google Scholar]
  100. Morita K, Hama Y, Izume T, Tamura N, Ueno T et al. 2018. Genome-wide CRISPR screen identifies TMEM41B as a gene required for autophagosome formation. J. Cell Biol. 217:3817–28
    [Google Scholar]
  101. Motley AM, Nuttall JM, Hettema EH 2012. Pex3-anchored Atg36 tags peroxisomes for degradation in Saccharomyces cerevisiae. EMBO J 31:2852–68
    [Google Scholar]
  102. Murakawa T, Yamaguchi O, Hashimoto A, Hikoso S, Takeda T et al. 2015. Bcl-2-like protein 13 is a mammalian Atg32 homologue that mediates mitophagy and mitochondrial fragmentation. Nat. Commun. 6:7527
    [Google Scholar]
  103. Nakatogawa H, Suzuki K, Kamada Y, Ohsumi Y 2009. Dynamics and diversity in autophagy mechanisms: lessons from yeast. Nat. Rev. Mol. Cell Biol. 10:458–67
    [Google Scholar]
  104. Nazarko TY, Ozeki K, Till A, Ramakrishnan G, Lotfi P et al. 2014. Peroxisomal Atg37 binds Atg30 or palmitoyl-CoA to regulate phagophore formation during pexophagy. J. Cell Biol. 204:541–57
    [Google Scholar]
  105. Nguyen TN, Padman BS, Usher J, Oorschot V, Ramm G, Lazarou M 2016. Atg8 family LC3/GABARAP proteins are crucial for autophagosome-lysosome fusion but not autophagosome formation during PINK1/Parkin mitophagy and starvation. J. Cell Biol. 215:857–74
    [Google Scholar]
  106. Ni HM, Woolbright BL, Williams J, Copple B, Cui W et al. 2014. Nrf2 promotes the development of fibrosis and tumorigenesis in mice with defective hepatic autophagy. J. Hepatol. 61:617–25
    [Google Scholar]
  107. Nishida Y, Arakawa S, Fujitani K, Yamaguchi H, Mizuta T et al. 2009. Discovery of Atg5/Atg7-independent alternative macroautophagy. Nature 461:654–58
    [Google Scholar]
  108. Noad J, von der Malsburg A, Pathe C, Michel MA, Komander D, Randow F 2017. LUBAC-synthesized linear ubiquitin chains restrict cytosol-invading bacteria by activating autophagy and NF-κB. Nat. Microbiol. 2:17063
    [Google Scholar]
  109. Noda NN, Ohsumi Y, Inagaki F 2010. Atg8-family interacting motif crucial for selective autophagy. FEBS Lett 584:1379–85
    [Google Scholar]
  110. Noda T. 2017. Autophagy in the context of the cellular membrane-trafficking system: the enigma of Atg9 vesicles. Biochem. Soc. Trans. 45:1323–31
    [Google Scholar]
  111. Noda T, Fujita N, Yoshimori T 2009. The late stages of autophagy: How does the end begin?. Cell Death Differ 16:984–90
    [Google Scholar]
  112. Novak I, Kirkin V, McEwan DG, Zhang J, Wild P et al. 2010. Nix is a selective autophagy receptor for mitochondrial clearance. EMBO Rep 11:45–51
    [Google Scholar]
  113. Okamoto K, Kondo-Okamoto N, Ohsumi Y 2009. Mitochondria-anchored receptor Atg32 mediates degradation of mitochondria via selective autophagy. Dev. Cell 17:87–97
    [Google Scholar]
  114. Oku M, Sakai Y. 2018. Three distinct types of microautophagy based on membrane dynamics and molecular machineries. BioEssays 40:e1800008
    [Google Scholar]
  115. Onodera J, Ohsumi Y. 2005. Autophagy is required for maintenance of amino acid levels and protein synthesis under nitrogen starvation. J. Biol. Chem. 280:31582–86
    [Google Scholar]
  116. Palikaras K, Lionaki E, Tavernarakis N 2018. Mechanisms of mitophagy in cellular homeostasis, physiology and pathology. Nat. Cell Biol. 20:1013–22
    [Google Scholar]
  117. Pankiv S, Clausen TH, Lamark T, Brech A, Bruun JA et al. 2007. p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy. J. Biol. Chem. 282:24131–45
    [Google Scholar]
  118. Papadopoulos C, Kirchner P, Bug M, Grum D, Koerver L et al. 2017. VCP/p97 cooperates with YOD1, UBXD1 and PLAA to drive clearance of ruptured lysosomes by autophagy. EMBO J 36:135–50
    [Google Scholar]
  119. Papadopoulos C, Meyer H. 2017. Detection and clearance of damaged lysosomes by the endo-lysosomal damage response and lysophagy. Curr. Biol. 27:R1330–41
    [Google Scholar]
  120. Pickles S, Vigie P, Youle RJ 2018. Mitophagy and quality control mechanisms in mitochondrial maintenance. Curr. Biol. 28:R170–85
    [Google Scholar]
  121. Pickrell AM, Huang CH, Kennedy SR, Ordureau A, Sideris DP et al. 2015. Endogenous Parkin preserves dopaminergic substantia nigral neurons following mitochondrial DNA mutagenic stress. Neuron 87:371–81
    [Google Scholar]
  122. Poillet-Perez L, Xie X, Zhan L, Yang Y, Sharp DW et al. 2018. Autophagy maintains tumour growth through circulating arginine. Nature 563:569–73
    [Google Scholar]
  123. Politi Y, Gal L, Kalifa Y, Ravid L, Elazar Z, Arama E 2014. Paternal mitochondrial destruction after fertilization is mediated by a common endocytic and autophagic pathway in Drosophila. . Dev. Cell 29:305–20
    [Google Scholar]
  124. Rambold AS, Cohen S, Lippincott-Schwartz J 2015. Fatty acid trafficking in starved cells: regulation by lipid droplet lipolysis, autophagy, and mitochondrial fusion dynamics. Dev. Cell 32:678–92
    [Google Scholar]
  125. Rambold AS, Kostelecky B, Elia N, Lippincott-Schwartz J 2011. Tubular network formation protects mitochondria from autophagosomal degradation during nutrient starvation. PNAS 108:10190–95
    [Google Scholar]
  126. Randow F, Youle RJ. 2014. Self and nonself: how autophagy targets mitochondria and bacteria. Cell Host Microbe 15:403–11
    [Google Scholar]
  127. Ravenhill BJ, Boyle KB, von Muhlinen N, Ellison CJ, Masson GR et al. 2019. The cargo receptor NDP52 initiates selective autophagy by recruiting the ULK complex to cytosol-invading bacteria. Mol. Cell 74:320–29.e6
    [Google Scholar]
  128. Richter B, Sliter DA, Herhaus L, Stolz A, Wang C et al. 2016. Phosphorylation of OPTN by TBK1 enhances its binding to Ub chains and promotes selective autophagy of damaged mitochondria. PNAS 113:4039–44
    [Google Scholar]
  129. Rogov VV, Stolz A, Ravichandran AC, Rios-Szwed DO, Suzuki H et al. 2017. Structural and functional analysis of the GABARAP interaction motif (GIM). EMBO Rep 18:1382–96
    [Google Scholar]
  130. Rojansky R, Cha MY, Chan DC 2016. Elimination of paternal mitochondria in mouse embryos occurs through autophagic degradation dependent on PARKIN and MUL1. eLife 5:e17896
    [Google Scholar]
  131. Saito T, Ichimura Y, Taguchi K, Suzuki T, Mizushima T et al. 2016. p62/Sqstm1 promotes malignancy of HCV-positive hepatocellular carcinoma through Nrf2-dependent metabolic reprogramming. Nat. Commun. 7:12030
    [Google Scholar]
  132. Saito T, Kuma A, Sugiura Y, Ichimura Y, Obata M et al. 2019. Autophagy regulates lipid metabolism through selective turnover of NCoR1. Nat. Commun. 10:1567
    [Google Scholar]
  133. Sánchez-Martín P, Komatsu M. 2018. p62/SQSTM1—steering the cell through health and disease. J. Cell Sci. 131:jcs222836
    [Google Scholar]
  134. Sargent G, van Zutphen T, Shatseva T, Zhang L, Di Giovanni V et al. 2016. PEX2 is the E3 ubiquitin ligase required for pexophagy during starvation. J. Cell Biol. 214:677–90
    [Google Scholar]
  135. Sato M, Sato K. 2011. Degradation of paternal mitochondria by fertilization-triggered autophagy in C. elegans embryos. Science 334:1141–44
    [Google Scholar]
  136. Sato M, Sato K, Tomura K, Kosako H, Sato K 2018. The autophagy receptor ALLO-1 and the IKKE-1 kinase control clearance of paternal mitochondria in Caenorhabditis elegans. Nat. Cell Biol. 20:81–91
    [Google Scholar]
  137. Schweers RL, Zhang J, Randall MS, Loyd MR, Li W et al. 2007. NIX is required for programmed mitochondrial clearance during reticulocyte maturation. PNAS 104:19500–5
    [Google Scholar]
  138. Shibata M, Yoshimura K, Furuya N, Koike M, Ueno T et al. 2009. The MAP1-LC3 conjugation system is involved in lipid droplet formation. Biochem. Biophys. Res. Commun. 382:419–23
    [Google Scholar]
  139. Shoemaker CJ, Huang TQ, Weir NR, Polyakov N, Schultz SW et al. 2019. CRISPR screening using an expanded toolkit of autophagy reporters identifies TMEM41B as a novel autophagy factor. PLOS Biol 17:4e2007044
    [Google Scholar]
  140. Singh R, Kaushik S, Wang Y, Xiang Y, Novak I et al. 2009. Autophagy regulates lipid metabolism. Nature 458:1131–35
    [Google Scholar]
  141. Sliter DA, Martinez J, Hao L, Chen X, Sun N et al. 2018. Parkin and PINK1 mitigate STING-induced inflammation. Nature 561:258–62
    [Google Scholar]
  142. Smith MD, Harley ME, Kemp AJ, Wills J, Lee M et al. 2018. CCPG1 is a non-canonical autophagy cargo receptor essential for ER-phagy and pancreatic ER proteostasis. Dev. Cell 44:217–32.e11
    [Google Scholar]
  143. Solvik T, Debnath J. 2016. At the crossroads of autophagy and infection: noncanonical roles for ATG proteins in viral replication. J. Cell Biol. 214:503–5
    [Google Scholar]
  144. Song WH, Yi YJ, Sutovsky M, Meyers S, Sutovsky P 2016. Autophagy and ubiquitin-proteasome system contribute to sperm mitophagy after mammalian fertilization. PNAS 113:E5261–70
    [Google Scholar]
  145. Soreng K, Neufeld TP, Simonsen A 2018. Membrane trafficking in autophagy. Int. Rev. Cell Mol. Biol. 336:1–92
    [Google Scholar]
  146. Sousa CM, Biancur DE, Wang X, Halbrook CJ, Sherman MH et al. 2016. Pancreatic stellate cells support tumour metabolism through autophagic alanine secretion. Nature 536:479–83
    [Google Scholar]
  147. Sun D, Wu R, Zheng J, Li P, Yu L 2018. Polyubiquitin chain-induced p62 phase separation drives autophagic cargo segregation. Cell Res 28:405–15
    [Google Scholar]
  148. Suzuki K, Morimoto M, Kondo C, Ohsumi Y 2011. Selective autophagy regulates insertional mutagenesis by the Ty1 retrotransposon in Saccharomyces cerevisiae. Dev. Cell 21:358–65
    [Google Scholar]
  149. Suzuki K, Nakamura S, Morimoto M, Fujii K, Noda NN et al. 2014. Proteomic profiling of autophagosome cargo in Saccharomyces cerevisiae. PLOS ONE 9:e91651
    [Google Scholar]
  150. Suzuki SW, Onodera J, Ohsumi Y 2011. Starvation induced cell death in autophagy-defective yeast mutants is caused by mitochondria dysfunction. PLOS ONE 6:e17412
    [Google Scholar]
  151. Takahashi Y, He H, Tang Z, Hattori T, Liu Y et al. 2018. An autophagy assay reveals the ESCRT-III component CHMP2A as a regulator of phagophore closure. Nat. Commun. 9:2855
    [Google Scholar]
  152. Takamura A, Komatsu M, Hara T, Sakamoto A, Kishi C et al. 2011. Autophagy-deficient mice develop multiple liver tumors. Genes Dev 25:795–800
    [Google Scholar]
  153. 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. 119:301–11
    [Google Scholar]
  154. Thurston TL, Ryzhakov G, Bloor S, von Muhlinen N, Randow F 2009. The TBK1 adaptor and autophagy receptor NDP52 restricts the proliferation of ubiquitin-coated bacteria. Nat. Immunol. 10:1215–21
    [Google Scholar]
  155. Thurston TL, Wandel MP, von Muhlinen N, Foeglein A, Randow F 2012. Galectin 8 targets damaged vesicles for autophagy to defend cells against bacterial invasion. Nature 482:414–18
    [Google Scholar]
  156. Tian Y, Li Z, Hu W, Ren H, Tian E et al. 2010. C. elegans screen identifies autophagy genes specific to multicellular organisms. Cell 141:1042–55
    [Google Scholar]
  157. Tsuboyama K, Koyama-Honda I, Sakamaki Y, Koike M, Morishita H, Mizushima N 2016. The ATG conjugation systems are important for degradation of the inner autophagosomal membrane. Science 354:1036–41
    [Google Scholar]
  158. Tsukada M, Ohsumi Y. 1993. Isolation and characterization of autophagy-defective mutants of Saccharomyces cerevisiae. FEBS Lett 333:169–74
    [Google Scholar]
  159. Tsukamoto S, Kuma A, Murakami M, Kishi C, Yamamoto A, Mizushima N 2008. Autophagy is essential for preimplantation development of mouse embryos. Science 321:117–20
    [Google Scholar]
  160. Tumbarello DA, Manna PT, Allen M, Bycroft M, Arden SD et al. 2015. The autophagy receptor TAX1BP1 and the molecular motor myosin VI are required for clearance of Salmonella typhimurium by autophagy. PLOS Pathog 11:e1005174 Correction. 2016. PLOS Pathog. 12:1005433
    [Google Scholar]
  161. Turco E, Witt M, Abert C, Bock-Bierbaum T, Su MY et al. 2019. FIP200 claw domain binding to p62 promotes autophagosome formation at ubiquitin condensates. Mol. Cell 74:330–46.e11
    [Google Scholar]
  162. Vargas JNS, Wang C, Bunker E, Hao L, Maric D et al. 2019. Spatiotemporal control of ULK1 activation by NDP52 and TBK1 during selective autophagy. Mol. Cell 74:347–62.e6
    [Google Scholar]
  163. von Muhlinen N, Akutsu M, Ravenhill BJ, Foeglein A, Bloor S et al. 2012. LC3C, bound selectively by a noncanonical LIR motif in NDP52, is required for antibacterial autophagy. Mol. Cell 48:329–42
    [Google Scholar]
  164. Wei Y, Chiang WC, Sumpter R Jr, Mishra P, Levine B 2017. Prohibitin 2 is an inner mitochondrial membrane mitophagy receptor. Cell 168:224–38.e10
    [Google Scholar]
  165. Wild P, Farhan H, McEwan DG, Wagner S, Rogov VV et al. 2011. Phosphorylation of the autophagy receptor optineurin restricts Salmonella growth. Science 333:228–33
    [Google Scholar]
  166. Wong YC, Holzbaur EL. 2014. Optineurin is an autophagy receptor for damaged mitochondria in parkin-mediated mitophagy that is disrupted by an ALS-linked mutation. PNAS 111:E4439–48
    [Google Scholar]
  167. Wyant GA, Abu-Remaileh M, Frenkel EM, Laqtom NN, Dharamdasani V et al. 2018. NUFIP1 is a ribosome receptor for starvation-induced ribophagy. Science 360:751–58
    [Google Scholar]
  168. Yamashita S, Abe K, Tatemichi Y, Fujiki Y 2014. The membrane peroxin PEX3 induces peroxisome-ubiquitination-linked pexophagy. Autophagy 10:1549–64
    [Google Scholar]
  169. Yang A, Herter-Sprie G, Zhang H, Lin EY, Biancur D et al. 2018. Autophagy sustains pancreatic cancer growth through both cell-autonomous and nonautonomous mechanisms. Cancer Discov 8:276–87
    [Google Scholar]
  170. Yang H, Ni HM, Guo F, Ding Y, Shi YH et al. 2016. Sequestosome 1/p62 protein is associated with autophagic removal of excess hepatic endoplasmic reticulum in mice. J. Biol. Chem. 291:18663–74
    [Google Scholar]
  171. Yoshida Y, Yasuda S, Fujita T, Hamasaki M, Murakami A et al. 2017. Ubiquitination of exposed glycoproteins by SCFFBXO27 directs damaged lysosomes for autophagy. PNAS 114:8574–79
    [Google Scholar]
  172. Yoshii SR, Kishi C, Ishihara N, Mizushima N 2011. Parkin mediates proteasome-dependent protein degradation and rupture of the outer mitochondrial membrane. J. Biol. Chem. 286:19630–40
    [Google Scholar]
  173. Zachari M, Ganley IG. 2017. The mammalian ULK1 complex and autophagy initiation. Essays Biochem 61:585–96
    [Google Scholar]
  174. Zaffagnini G, Savova A, Danieli A, Romanov J, Tremel S et al. 2018. p62 filaments capture and present ubiquitinated cargos for autophagy. EMBO J 37:e98308
    [Google Scholar]
  175. Zhang G, Wang Z, Du Z, Zhang H 2018. mTOR regulates phase separation of PGL granules to modulate their autophagic degradation. Cell 174:1492–506.e22
    [Google Scholar]
  176. Zhang J, Tripathi DN, Jing J, Alexander A, Kim J et al. 2015. ATM functions at the peroxisome to induce pexophagy in response to ROS. Nat. Cell Biol. 17:1259–69
    [Google Scholar]
  177. Zhang Y, Yan L, Zhou Z, Yang P, Tian E et al. 2009. SEPA-1 mediates the specific recognition and degradation of P granule components by autophagy in C. elegans. Cell 136:308–21
    [Google Scholar]
  178. Zhao YG, Zhang H. 2018. Autophagosome maturation: an epic journey from the ER to lysosomes. J. Cell Biol. 218:757–70
    [Google Scholar]
  179. Zheng YT, Shahnazari S, Brech A, Lamark T, Johansen T, Brumell JH 2009. The adaptor protein p62/SQSTM1 targets invading bacteria to the autophagy pathway. J. Immunol. 183:5909–16
    [Google Scholar]
  180. Zhou Q, Li H, Li H, Nakagawa A, Lin JL et al. 2016. Mitochondrial endonuclease G mediates breakdown of paternal mitochondria upon fertilization. Science 353:394–99
    [Google Scholar]
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