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Emerging roles of ATG9/ATG9A in autophagy: implications for cell and neurobiology

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Choi, Jiyoung, Jang, Haeun, Xuan, Zhao, Park, Daehun·2024·Autophagy
DOI 10.1080/15548627.2024.2384349PMC PMC11572220
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Abstract

Atg9, the only transmembrane protein among many autophagy-related proteins, was first identified in the year 2000 in yeast. Two homologs of Atg9, ATG9A and ATG9B, have been found in mammals. While ATG9B shows a tissue-specific expression pattern, such as in the placenta and pituitary gland, ATG9A is ubiquitously expressed. Additionally, ATG9A deficiency leads to severe defects not only at the molecular and cellular levels but also at the organismal level, suggesting key and fundamental roles for ATG9A. The subcellular localization of ATG9A on small vesicles and its functional relevance to autophagy have suggested a potential role for ATG9A in the lipid supply during autophagosome biogenesis. Nevertheless, the precise role of ATG9A in the autophagic process has remained a long-standing mystery, especially in neurons. Recent findings, however, including structural, proteomic, and biochemical analyses, have provided new insights into its function in the expansion of the phagophore membrane. In this review, we aim to understand various aspects of ATG9 (in invertebrates and plants)/ATG9A (in mammals), including its localization, trafficking, and other functions, in nonneuronal cells and neurons by comparing recent discoveries related to ATG9/ATG9A and proposing directions for future research.Abbreviation: AP-4: adaptor protein complex 4; ATG: autophagy related; cKO: conditional knockout; CLA-1: CLArinet (functional homolog of cytomatrix at the active zone proteins piccolo and fife); cryo-EM: cryogenic electron microscopy; ER: endoplasmic reticulum; KO: knockout; PAS: phagophore assembly site; PtdIns3K: class III phosphatidylinositol 3-kinase; PtdIns3P: phosphatidylinositol-3-phosphate; RB1CC1/FIP200: RB1 inducible coiled-coil 1; SV: synaptic vesicle; TGN: trans-Golgi network; ULK: unc-51 like autophagy activating kinase; WIPI2: WD repeat domain, phosphoinositide interacting 2.

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  • ATG9A is not incorporated into autophagosomes and plays an essential role in their formation, expansion and closure.

    “ATG9A, which itself is not incorporated into autophagosomes, is known to play an essential role for their formation, expansion and closure [47, 48].”

    From miRNA family miR-29 inhibits PINK1-PRKN signaling via ATG9A (2026) · cites this paper as [47]

    The 'Role of ATG9/ATG9A in autophagy' section says ATG9A is believed to interact with autophagosomes without being incorporated into them, and links it to phagophore expansion. The membrane-expansion models section also supports a role in early formation. The copy does not establish a role in autophagosome closure, and its wording is more tentative than 'is known to play an essential role' throughout. (LLM, conf=0.86)

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  1. [1]Klionsky DJ, Emr SD. Autophagy as a regulated pathway of cellular degradation. Science. 2000 Dec 1; 290(5497): 1717– 1721. doi: 10.1126/science.290.5497.1717 11099404 PMC2732363 · DOI
  2. [4]Mortimore GE, Pösö AR. Intracellular protein catabolism and its control during nutrient deprivation and supply. Annu Rev Nutr. 1987; 7(1): 539– 564. doi: 10.1146/annurev.nu.07.070187.002543 3300746 · DOI
  3. [5]Meijer AJ, Codogno P. Regulation and role of autophagy in mammalian cells. Int J Biochem Cell Biol. 2004 Dec; 36(12): 2445– 2462. doi: 10.1016/j.biocel.2004.02.002 15325584 · DOI
  4. [6]Burman C, Ktistakis NT. Autophagosome formation in mammalian cells. Semin Immunopathol. 2010 Dec 01; 32(4): 397– 413. doi: 10.1007/s00281-010-0222-z 20740284 · DOI
  5. [8]Uchiyama Y, Shibata M, Koike M, et al. Autophagy-physiology and pathophysiology. Histochem Cell Biol. 2008 Apr; 129(4): 407– 420. doi: 10.1007/s00418-008-0406-y 18320203 PMC2668654 · DOI
  6. [9]Mercer TJ, Gubas A, Tooze SA. A molecular perspective of mammalian autophagosome biogenesis. J Biol Chem. 2018 Apr 13; 293(15): 5386– 5395. doi: 10.1074/jbc.R117.810366 29371398 PMC5900756 · DOI
  7. [10]Nakatogawa H, Suzuki K, Kamada Y, et al. Dynamics and diversity in autophagy mechanisms: lessons from yeast. Nat Rev Mol Cell Biol. 2009 Jul; 10(7): 458– 467. doi: 10.1038/nrm2708 19491929 · DOI
  8. [11]Melia TJ, Lystad AH, Simonsen A. Autophagosome biogenesis: from membrane growth to closure. J Cell Biol. 2020 Jun 1; 219(6). doi: 10.1083/jcb.202002085 PMC7265318 32357219 · DOI
  9. [12]Nakatogawa H. Mechanisms governing autophagosome biogenesis. Nat Rev Mol Cell Biol. 2020 Aug 01; 21(8): 439– 458. doi: 10.1038/s41580-020-0241-0 32372019 · DOI
  10. [13]Matoba K, Noda NN. Structural catalog of core atg proteins opens new era of autophagy research. J Biochem. 2021 Jul 3; 169(5): 517– 525. doi: 10.1093/jb/mvab017 33576807 · DOI
  11. [14]Yamamoto H, Kakuta S, Watanabe TM, et al. Atg9 vesicles are an important membrane source during early steps of autophagosome formation. J Cell Biol. 2012 Jul 23; 198(2): 219– 233. doi: 10.1083/jcb.201202061 22826123 PMC3410421 · DOI · Paper page
  12. [16]Noda T, Kim J, Huang WP, et al. Apg9p/Cvt7p is an integral membrane protein required for transport vesicle formation in the cvt and autophagy pathways. J Cell Biol. 2000 Feb 7; 148(3): 465– 480. doi: 10.1083/jcb.148.3.465 10662773 PMC2174799 · DOI
  13. [17]Edgar RC. MUSCLE: multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res. 2004; 32(5): 1792– 1797. doi: 10.1093/nar/gkh340 15034147 PMC390337 · DOI · Paper page
  14. [18]Kumar S, Stecher G, Li M, et al. MEGA X: molecular evolutionary genetics analysis across computing platforms. Mol Biol Evol. 2018 Jun 1; 35(6): 1547– 1549. doi: 10.1093/molbev/msy096 29722887 PMC5967553 · DOI
  15. [19]Bult CJ, Sternberg PW. The alliance of genome resources: transforming comparative genomics. Mamm Genome. 2023 Dec; 34(4): 531– 544. doi: 10.1007/s00335-023-10015-2 37666946 PMC10628019 · DOI
  16. [20]Martin FJ, Amode MR, Aneja A, et al. Ensembl 2023. Nucleic Acids Res. 2023; 51(D1): D933– D941. doi: 10.1093/nar/gkac958 36318249 PMC9825606 · DOI
  17. [21]Chiduza GN, Garza-Garcia A, Almacellas E, et al. ATG9B is a tissue-specific homotrimeric lipid scramblase that can compensate for ATG9A. Autophagy. 2023 Nov; 20(3): 1– 20. doi: 10.1080/15548627.2023.2275905 37938170 PMC10936676 · DOI
  18. [22]Robb GB, Carson AR, Tai SC, et al. Post-transcriptional regulation of endothelial nitric-oxide synthase by an overlapping antisense mRNA transcript. J Biol Chem. 2004 Sep 3; 279(36): 37982– 37996. doi: 10.1074/jbc.M400271200 15234981 · DOI
  19. [23]Wang N, Tan HY, Li S, et al. Atg9b deficiency suppresses autophagy and potentiates endoplasmic reticulum stress-associated hepatocyte apoptosis in Hepatocarcinogenesis. Theranostics. 2017; 7(8): 2325– 2338. doi: 10.7150/thno.18225 28740555 PMC5505064 · DOI
  20. [24]Tamura H, Shibata M, Koike M, et al. Atg9A protein, an autophagy-related membrane protein, is localized in the neurons of mouse brains. J Histochem Cytochem. 2010 May; 58(5): 443– 453. doi: 10.1369/jhc.2010.955690 20124090 PMC2857816 · DOI
  21. [25]Yamada T, Carson AR, Caniggia I, et al. Endothelial nitric-oxide synthase antisense (NOS3AS) gene encodes an autophagy-related protein (APG9-like2) highly expressed in trophoblast. J Biol Chem. 2005 May 6; 280(18): 18283– 18290. doi: 10.1074/jbc.M413957200 15755735 · DOI
  22. [26]Mailler E, Guardia CM, Bai X, et al. The autophagy protein ATG9A enables lipid mobilization from lipid droplets. Nat Commun. 2021 Nov 19; 12(1): 6750. doi: 10.1038/s41467-021-26999-x 34799570 PMC8605025 · DOI
  23. [27]Zhang X, Li C, Wang D, et al. Aberrant methylation of ATG2B, ATG4D, ATG9A and ATG9B CpG island promoter is associated with decreased mRNA expression in sporadic breast carcinoma. Gene. 2016 Sep 30; 590(2): 285– 292. doi: 10.1016/j.gene.2016.05.036 27265029 · DOI
  24. [28]Young AR, Chan EY, Hu XW, et al. Starvation and ULK1-dependent cycling of mammalian Atg9 between the TGN and endosomes. J Cell Sci. 2006 Sep 15; 119(Pt 18): 3888– 3900. doi: 10.1242/jcs.03172 16940348 · DOI · Paper page
  25. [29]Saitoh T, Fujita N, Hayashi T, et al. Atg9a controls dsDNA-driven dynamic translocation of STING and the innate immune response. Proc Natl Acad Sci U S A. [ 2009 Dec 8]; 106(49): 20842– 20846. doi: 10.1073/pnas.0911267106 19926846 PMC2791563 · DOI · Paper page
  26. [30]Kojima T, Yamada T, Akaishi R, et al. Role of the Atg9a gene in intrauterine growth and survival of fetal mice. Reprod Biol. 2015 Sep; 15(3): 131– 138. doi: 10.1016/j.repbio.2015.05.001 26370455 · DOI
  27. [31]Mattera R, Park SY, De Pace R, et al. AP-4 mediates export of ATG9A from the trans-Golgi network to promote autophagosome formation. Proc Natl Acad Sci U S A. [ 2017 Dec 12]; 114(50): E10697– E10706. doi: 10.1073/pnas.1717327114 29180427 PMC5740629 · DOI
  28. [32]Kishi-Itakura C, Koyama-Honda I, Itakura E, et al. Ultrastructural analysis of autophagosome organization using mammalian autophagy-deficient cells. J Cell Sci. [ 2014 Sep 15]; 127(Pt 18): 4089– 4102. doi: 10.1242/jcs.164293 25052093 · DOI
  29. [34]Runwal G, Stamatakou E, Siddiqi FH, et al. LC3-positive structures are prominent in autophagy-deficient cells. Sci Rep. 2019 July 12; 9(1): 10147. doi: 10.1038/s41598-019-46657-z 31300716 PMC6625982 · DOI · Paper page
  30. [35]Olivas TJ, Wu Y, Yu S, et al. ATG9 vesicles comprise the seed membrane of mammalian autophagosomes. J Cell Biol. 2023 Jul 3; 222(7). doi: 10.1083/jcb.202208088 PMC10148236 37115958 · DOI
  31. [36]Yamaguchi J, Suzuki C, Nanao T, et al. Atg9a deficiency causes axon-specific lesions including neuronal circuit dysgenesis. Autophagy. 2018; 14(5): 764– 777. doi: 10.1080/15548627.2017.1314897 28513333 PMC6070006 · DOI · Paper page
  32. [37]Pankiv S, Clausen TH, Lamark T, et al. p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy. J Biol Chem. 2007 08; 282(33): 24131– 24145. doi: 10.1074/jbc.M702824200 17580304 · DOI · Paper page
  33. [38]Son JH, Shim JH, Kim K-H, et al. Neuronal autophagy and neurodegenerative diseases. Exp Mol Med. 2012 Feb 01; 44(2): 89– 98. doi: 10.3858/emm.2012.44.2.031 22257884 PMC3296817 · DOI
  34. [39]Stavoe AKH, Holzbaur ELF. Autophagy in neurons. Annu Rev Cell Dev Biol. 2019 Oct 6; 35(1): 477– 500. doi: 10.1146/annurev-cellbio-100818-125242 31340124 PMC6996145 · DOI · Paper page
  35. [40]Lai LTF, Yu C, Wong JSK, et al. Subnanometer resolution cryo-EM structure of Arabidopsis thaliana ATG9. Autophagy. 2020 Mar; 16(3): 575– 583. doi: 10.1080/15548627.2019.1639300 31276439 PMC6999609 · DOI
  36. [42]Matoba K, Kotani T, Tsutsumi A, et al. Atg9 is a lipid scramblase that mediates autophagosomal membrane expansion. Nat Struct Mol Biol. 2020 Dec; 27(12): 1185– 1193. doi: 10.1038/s41594-020-00518-w 33106658 · DOI · Paper page
  37. [43]Malhotra N, Khatri S, Kumar A, et al. AI-based AlphaFold2 significantly expands the structural space of the autophagy pathway. Autophagy. 2023 Dec; 19(12): 3201– 3220. doi: 10.1080/15548627.2023.2238578 37516933 PMC10621275 · DOI
  38. [44]Berman HM, Westbrook J, Feng Z, et al. The protein data bank. Nucleic Acids Res. 2000; 28(1): 235– 242. doi: 10.1093/nar/28.1.235 10592235 PMC102472 · DOI · Paper page
  39. [45]Sehnal D, Bittrich S, Deshpande M, et al. Mol* viewer: modern web app for 3D visualization and analysis of large biomolecular structures. Nucleic Acids Res. 2021; 49(W1): W431– W437. doi: 10.1093/nar/gkab314 33956157 PMC8262734 · DOI · Paper page
  40. [46]Park D, Wu Y, Wang X, et al. Synaptic vesicle proteins and ATG9A self-organize in distinct vesicle phases within synapsin condensates. Nat Commun. 2023 Jan 28; 14(1): 455. doi: 10.1038/s41467-023-36081-3 36709207 PMC9884207 · DOI
  41. [47]van Vliet AR, Chiduza GN, Maslen SL, et al. ATG9A and ATG2A form a heteromeric complex essential for autophagosome formation. Mol Cell. 2022 Nov 17; 82(22): 4324– 4339 e8. doi: 10.1016/j.molcel.2022.10.017 36347259 · DOI
  42. [48]Noda NN. Atg2 and Atg9: intermembrane and interleaflet lipid transporters driving autophagy. Biochim Biophys Acta Mol Cell Biol Lipids. 2021 Aug; 1866(8): 158956. doi: 10.1016/j.bbalip.2021.158956 33932584 · DOI
  43. [49]Kakuta S, Yamaguchi J, Suzuki C, et al. Small GTPase Rab1B is associated with ATG9A vesicles and regulates autophagosome formation. Faseb J. 2017 Sep; 31(9): 3757– 3773. doi: 10.1096/fj.201601052R 28522593 · DOI
  44. [50]Orsi A, Razi M, Dooley HC, et al. Dynamic and transient interactions of Atg9 with autophagosomes, but not membrane integration, are required for autophagy. Mol Biol Cell. 2012 May; 23(10): 1860– 1873. doi: 10.1091/mbc.e11-09-0746 22456507 PMC3350551 · DOI
  45. [51]Imai K, Hao F, Fujita N, et al. Atg9A trafficking through the recycling endosomes is required for autophagosome formation. J Cell Sci. 2016 Oct 15; 129(20): 3781– 3791. doi: 10.1242/jcs.196196 27587839 · DOI
  46. [52]Puri C, Renna M, Bento CF, et al. Diverse autophagosome membrane sources coalesce in recycling endosomes. Cell. 2013 Sep 12; 154(6): 1285– 1299. doi: 10.1016/j.cell.2013.08.044 24034251 PMC3791395 · DOI
  47. [54]Majumder P, Edmison D, Rodger C, et al. AP-4 regulates neuronal lysosome composition, function, and transport via regulating export of critical lysosome receptor proteins at the trans-Golgi network. Mol Biol Cell. 2022 Oct 1; 33(12): ar102. doi: 10.1091/mbc.E21-09-0473 35976706 PMC9635302 · DOI
  48. [55]Davies AK, Itzhak DN, Edgar JR, et al. AP-4 vesicles contribute to spatial control of autophagy via RUSC-dependent peripheral delivery of ATG9A. Nat Commun. 2018 Sep 27; 9(1): 3958. doi: 10.1038/s41467-018-06172-7 30262884 PMC6160451 · DOI
  49. [56]De Pace R, Skirzewski M, Damme M, et al. Altered distribution of ATG9A and accumulation of axonal aggregates in neurons from a mouse model of AP-4 deficiency syndrome. PLOS Genet. 2018 Apr; 14(4): e1007363. doi: 10.1371/journal.pgen.1007363 29698489 PMC5940238 · DOI
  50. [57]Ivankovic D, Drew J, Lesept F, et al. Axonal autophagosome maturation defect through failure of ATG9A sorting underpins pathology in AP-4 deficiency syndrome. Autophagy. 2020 Mar; 16(3): 391– 407. doi: 10.1080/15548627.2019.1615302 31142229 PMC6999640 · DOI
  51. [58]Kannangara AR, Poole DM, McEwan CM, et al. BioID reveals an ATG9A interaction with ATG13-ATG101 in the degradation of p62/SQSTM1-ubiquitin clusters. EMBO Rep. 2021 Oct 5; 22(10): e51136. doi: 10.15252/embr.202051136 34369648 PMC8490997 · DOI
  52. [59]Binotti B, Ninov M, Cepeda AP, et al. ATG9 resides on a unique population of small vesicles in presynaptic nerve terminals. Autophagy. 2023 Oct; 20(4): 1– 19. doi: 10.1080/15548627.2023.2274204 37881948 PMC11062364 · DOI
  53. [60]Zhou C, Ma K, Gao R, et al. Regulation of mATG9 trafficking by src- and ULK1-mediated phosphorylation in basal and starvation-induced autophagy. Cell Res. 2017 Feb; 27(2): 184– 201. doi: 10.1038/cr.2016.146 27934868 PMC5339848 · DOI
  54. [61]Popovic D, Dikic I. TBC1D5 and the AP2 complex regulate ATG9 trafficking and initiation of autophagy. EMBO Rep. 2014 Apr; 15(4): 392– 401. doi: 10.1002/embr.201337995 24603492 PMC3989670 · DOI
  55. [62]Guo Y, Chang C, Huang R, et al. AP1 is essential for generation of autophagosomes from the trans-Golgi network. J Cell Sci. [ 2012 Apr 1]; 125(Pt 7): 1706– 1715. doi: 10.1242/jcs.093203 22328508 · DOI
  56. [63]Yang S, Park D, Manning L, et al. Presynaptic autophagy is coupled to the synaptic vesicle cycle via ATG-9. Neuron. 2022 Mar 2; 110(5): 824– 840 e10. doi: 10.1016/j.neuron.2021.12.031 35065714 PMC9017068 · DOI
  57. [65]Xuan Z, Yang S, Clark B, et al. The active zone protein clarinet regulates synaptic sorting of ATG-9 and presynaptic autophagy. PLOS Biol. 2023 Apr; 21(4): e3002030. doi: 10.1371/journal.pbio.3002030 37053235 PMC10101500 · DOI
  58. [66]Xuan Z, Colón-Ramos DA. The active zone protein CLA-1 (clarinet) bridges two subsynaptic domains to regulate presynaptic sorting of ATG-9. Autophagy. 2023 Oct; 19(10): 2807– 2808. doi: 10.1080/15548627.2023.2229227 37389488 PMC10472863 · DOI
  59. [67]Okerlund ND, Schneider K, Leal-Ortiz S, et al. Bassoon controls presynaptic autophagy through Atg5. Neuron. 2017 Feb 22; 93(4): 897– 913.e7. doi: 10.1016/j.neuron.2017.01.026 28231469 · DOI
  60. [68]Ke X, Bittencourt C, Van Tendeloo G. Possibilities and limitations of advanced transmission electron microscopy for carbon-based nanomaterials. Beilstein J Nanotechnol. 2015; 6: 1541– 1557. doi: 10.3762/bjnano.6.158 26425406 PMC4578338 · DOI · Paper page
  61. [69]Coumans F, Brisson A, Buzás E, et al. Methodological guidelines to study extracellular vesicles. Circ Res. 2017 May 12; 120: 1632– 1648. doi: 10.1161/CIRCRESAHA.117.309417 28495994 · DOI
  62. [70]Noda T. Autophagy in the context of the cellular membrane-trafficking system: the enigma of Atg9 vesicles. Biochem Soc Trans. 2017 Dec 15; 45(6): 1323– 1331. doi: 10.1042/BST20170128 29150528 PMC5730941 · DOI
  63. [71]Taoufiq Z, Ninov M, Villar-Briones A, et al. Hidden proteome of synaptic vesicles in the mammalian brain. Proc Natl Acad Sci USA. 2020 Dec 29; 117(52): 33586– 33596. doi: 10.1073/pnas.2011870117 33376223 PMC7776996 · DOI
  64. [72]Ren X, Nguyen TN, Lam WK, et al. Structural basis for ATG9A recruitment to the ULK1 complex in mitophagy initiation. Sci Adv. [ 2023 Feb 15]; 9(7): eadg2997. doi: 10.1126/sciadv.adg2997 36791199 PMC9931213 · DOI · Paper page
  65. [73]Nguyen A, Lugarini F, David C, et al. Metamorphic proteins at the basis of human autophagy initiation and lipid transfer. Mol Cell. 2023 Jun 15; 83(12): 2077– 2090 e12. doi: 10.1016/j.molcel.2023.04.026 37209685 · DOI
  66. [74]Merrill NM, Schipper JL, Karnes JB, et al. PI3K-C2α knockdown decreases autophagy and maturation of endocytic vesicles. PLOS ONE. 2017; 12(9): e0184909. doi: 10.1371/journal.pone.0184909 28910396 PMC5599018 · DOI
  67. [75]Ghanbarpour A, Valverde DP, Melia TJ, et al. A model for a partnership of lipid transfer proteins and scramblases in membrane expansion and organelle biogenesis. Proc Natl Acad Sci USA. 2021 Apr 20; 118(16). doi: 10.1073/pnas.2101562118 PMC8072408 33850023 · DOI
  68. [76]Suzuki K, Ohsumi Y. Current knowledge of the pre-autophagosomal structure (PAS). FEBS Lett. 2010 Apr 02; 584(7): 1280– 1286. doi: 10.1016/j.febslet.2010.02.001 20138172 · DOI
  69. [77]Ktistakis NT, Tooze SA. Digesting the expanding mechanisms of autophagy. Trends Cell Biol. 2016 Aug 01; 26(8): 624– 635. doi: 10.1016/j.tcb.2016.03.006 27050762 · DOI
  70. [78]Goldsmith J, Ordureau A, Harper JW, et al. Brain-derived autophagosome profiling reveals the engulfment of nucleoid-enriched mitochondrial fragments by basal autophagy in neurons. Neuron. [ 2022 Mar 16]; 110(6): 967– 976 e8. doi: 10.1016/j.neuron.2021.12.029 35051374 PMC8930448 · DOI
  71. [79]Karanasios E, Walker SA, Okkenhaug H, et al. Autophagy initiation by ULK complex assembly on ER tubulovesicular regions marked by ATG9 vesicles. Nat Commun. 2016 Aug 11; 7(1): 12420. doi: 10.1038/ncomms12420 27510922 PMC4987534 · DOI
  72. [80]Kageyama S, Omori H, Saitoh T, et al. The LC3 recruitment mechanism is separate from Atg9L1-dependent membrane formation in the autophagic response against Salmonella. Mol Biol Cell. 2011 Jul 1; 22(13): 2290– 2300. doi: 10.1091/mbc.e10-11-0893 21525242 PMC3128531 · DOI · Paper page
  73. [81]Holzer E, Martens S, Tulli S. The role of ATG9 vesicles in autophagosome biogenesis. J Mol Biol. 2024 Feb 10; 436(15): 168489. doi: 10.1016/j.jmb.2024.168489 38342428 · DOI
  74. [82]Valverde DP, Yu S, Boggavarapu V, et al. ATG2 transports lipids to promote autophagosome biogenesis. J Cell Biol. [ 2019 Jun 3]; 218(6): 1787– 1798. doi: 10.1083/jcb.201811139 30952800 PMC6548141 · DOI
  75. [83]Gomez-Sanchez R, Rose J, Guimaraes R, et al. Atg9 establishes Atg2-dependent contact sites between the endoplasmic reticulum and phagophores. J Cell Biol. 2018 Aug 6; 217(8): 2743– 2763. doi: 10.1083/jcb.201710116 29848619 PMC6080931 · DOI
  76. [84]Osawa T, Kotani T, Kawaoka T, et al. Atg2 mediates direct lipid transfer between membranes for autophagosome formation. Nat Struct Mol Biol. 2019 Apr; 26(4): 281– 288. doi: 10.1038/s41594-019-0203-4 30911189 · DOI
  77. [85]Graef M. Membrane tethering by the autophagy ATG2A-WIPI4 complex. Proc Natl Acad Sci U S A. 2018 Oct 16; 115(42): 10540– 10541. doi: 10.1073/pnas.1814759115 30275332 PMC6196487 · DOI
  78. [86]Zheng J-X, Li Y, Ding Y-H, et al. Architecture of the ATG2B-WDR45 complex and an aromatic Y/HF motif crucial for complex formation. Autophagy. 2017 Nov 02; 13(11): 1870– 1883. doi: 10.1080/15548627.2017.1359381 28820312 PMC5788475 · DOI
  79. [87]Vargas Duarte P, Reggiori F. The organization and function of the phagophore-ER membrane contact sites. Contact (Thousand Oaks). Contact. 2023 Jan-Dec; 6: 25152564231183898. doi: 10.1177/25152564231183898 37465355 PMC10350784 · DOI
  80. [88]Moretti F, Bergman P, Dodgson S, et al. TMEM41B is a novel regulator of autophagy and lipid mobilization. EMBO Rep. 2018 Sep 01; 19(9): e45889. doi: 10.15252/embr.201845889 30126924 PMC6123663 · DOI
  81. [89]Morita K, Hama Y, Izume T, et al. Genome-wide CRISPR screen identifies TMEM41B as a gene required for autophagosome formation. J Cell Biol. 2018; 217(11): 3817– 3828. doi: 10.1083/jcb.201804132 30093494 PMC6219718 · DOI
  82. [90]Shoemaker CJ, Huang TQ, Weir NR, et al. CRISPR screening using an expanded toolkit of autophagy reporters identifies TMEM41B as a novel autophagy factor. PLOS Biol. 2019; 17(4): e2007044. doi: 10.1371/journal.pbio.2007044 30933966 PMC6459555 · DOI
  83. [91]Chen A, Ding WX, Ni HM. Scramblases as regulators of autophagy and lipid homeostasis: implications for NAFLD. Autophagy Rep. 2022; 1(1): 143– 160. doi: 10.1080/27694127.2022.2055724 35509327 PMC9066413 · DOI
  84. [92]Sawa-Makarska J, Baumann V, Coudevylle N, et al. Reconstitution of autophagosome nucleation defines Atg9 vesicles as seeds for membrane formation. Science. 2020 Sep 4; 369(6508). doi: 10.1126/science.aaz7714 PMC7610778 32883836 · DOI
  85. [93]Broadbent DG, Barnaba C, Perez GI, et al. Quantitative analysis of autophagy reveals the role of ATG9 and ATG2 in autophagosome formation. J Cell Biol. 2023 Jul 3; 222(7). doi: 10.1083/jcb.202210078 PMC10148237 37115157 · DOI
  86. [94]Pfisterer SG, Bakula D, Frickey T, et al. Lipid droplet and early autophagosomal membrane targeting of Atg2A and Atg14L in human tumor cells[S]. J Lipid Res. 2014 July 01; 55(7): 1267– 1278. doi: 10.1194/jlr.M046359 24776541 PMC4076084 · DOI
  87. [95]Velikkakath AKG, Nishimura T, Oita E, et al. Mammalian Atg2 proteins are essential for autophagosome formation and important for regulation of size and distribution of lipid droplets. Mol Biol Cell. 2012; 23(5): 896– 909. doi: 10.1091/mbc.e11-09-0785 22219374 PMC3290647 · DOI
  88. [96]Bradberry MM, Mishra S, Zhang Z, et al. Rapid and gentle immunopurification of brain synaptic vesicles. J Neurosci. 2022 Apr 27; 42(17): 3512– 3522. doi: 10.1523/JNEUROSCI.2521-21.2022 35296545 PMC9053850 · DOI
  89. [97]Chantranupong L, Saulnier JL, Wang W, et al. Rapid purification and metabolomic profiling of synaptic vesicles from mammalian brain. Elife. 2020 Oct 12; 9: e59699. doi: 10.7554/eLife.59699 33043885 PMC7575323 · DOI
  90. [98]Hanna MG, Suen PH, Wu Y, et al. SHIP164 is a chorein motif lipid transfer protein that controls endosome–golgi membrane traffic. J Cell Biol. 2022; 221(6): e202111018. doi: 10.1083/jcb.202111018 35499567 PMC9067936 · DOI · Paper page
  91. [99]van Vliet AR, Jefferies HBJ, Faull PA, et al. Exploring the ATG9A interactome uncovers interaction with VPS13A. J Cell Sci. 2024; 137(4): jcs261081. doi: 10.1242/jcs.261081 38294121 PMC10911177 · DOI
  92. [100]Nishida Y, Nakamura M, Urata Y, et al. Novel pathogenic VPS13A gene mutations in Japanese patients with chorea-acanthocytosis. Neurol Genet. 2019 Jun; 5(3): e332. doi: 10.1212/NXG.0000000000000332 31192303 PMC6515943 · DOI
  93. [101]García-García E, Chaparro-Cabanillas N, Coll-Manzano A, et al. Unraveling the spatiotemporal distribution of VPS13A in the mouse brain. Int J Mol Sci. 2021 Dec 1; 22(23): 13018. doi: 10.3390/ijms222313018 34884823 PMC8657609 · DOI
  94. [102]Hayashi-Nishino M, Fujita N, Noda T, et al. A subdomain of the endoplasmic reticulum forms a cradle for autophagosome formation. Nat Cell Biol. 2009 Dec; 11(12): 1433– 1437. doi: 10.1038/ncb1991 19898463 · DOI
  95. [103]Axe EL, Walker SA, Manifava M, et al. Autophagosome formation from membrane compartments enriched in phosphatidylinositol 3-phosphate and dynamically connected to the endoplasmic reticulum. J Cell Biol. 2008 Aug 25; 182(4): 685– 701. doi: 10.1083/jcb.200803137 18725538 PMC2518708 · DOI · Paper page
  96. [104]Walker SA, Ktistakis NT. Autophagosome biogenesis machinery. J Mol Biol. 2020 Apr 03; 432(8): 2449– 2461. doi: 10.1016/j.jmb.2019.10.027 31705882 · DOI
  97. [105]Hailey DW, Rambold AS, Satpute-Krishnan P, et al. Mitochondria supply membranes for autophagosome biogenesis during starvation. Cell. 2010 May 14; 141(4): 656– 667. doi: 10.1016/j.cell.2010.04.009 20478256 PMC3059894 · DOI
  98. [106]Hamasaki M, Furuta N, Matsuda A, et al. Autophagosomes form at ER–mitochondria contact sites. Nature. 2013 Mar 01; 495(7441): 389– 393. doi: 10.1038/nature11910 23455425 · DOI
  99. [107]Wen JK, Wang YT, Chan CC, et al. Atg9 antagonizes TOR signaling to regulate intestinal cell growth and epithelial homeostasis in Drosophila. Elife. 2017 Nov 16; 6. doi: 10.7554/eLife.29338 PMC5690286 29144896 · DOI
  100. [108]Hanaoka H, Noda T, Shirano Y, et al. Leaf senescence and starvation-induced chlorosis are accelerated by the disruption of an Arabidopsis autophagy gene. Plant Physiol. 2002 Jul; 129(3): 1181– 1193. doi: 10.1104/pp.011024 12114572 PMC166512 · DOI
  101. [109]Tóth ML, Sigmond T, Borsos E, et al. Longevity pathways converge on autophagy genes to regulate life span in Caenorhabditis elegans. Autophagy. 2008 Apr; 4(3): 330– 338. doi: 10.4161/auto.5618 18219227 · DOI
  102. [110]Hashimoto Y, Ookuma S, Nishida E. Lifespan extension by suppression of autophagy genes in caenorhabditis elegans. Genes Cells. 2009 Jun; 14(6): 717– 726. doi: 10.1111/j.1365-2443.2009.01306.x 19469880 · DOI
  103. [111]Hensel LL, Grbić V, Baumgarten DA, et al. Developmental and age-related processes that influence the longevity and senescence of photosynthetic tissues in arabidopsis. Plant Cell. 1993; 5(5): 553– 564. doi: 10.1105/tpc.5.5.553 8518555 PMC160293 · DOI
  104. [112]Saitoh T, Fujita N, Jang MH, et al. Loss of the autophagy protein Atg16L1 enhances endotoxin-induced IL-1beta production. Nature. 2008 Nov 13; 456(7219): 264– 268. doi: 10.1038/nature07383 18849965 · DOI
  105. [114]Kuma A, Hatano M, Matsui M, et al. The role of autophagy during the early neonatal starvation period. Nature. 2004 Dec 23; 432(7020): 1032– 1036. doi: 10.1038/nature03029 15525940 · DOI · Paper page
  106. [115]Kiss V, Jipa A, Varga K, et al. Drosophila Atg9 regulates the actin cytoskeleton via interactions with profilin and ena. Cell Death Differ. 2020 May; 27(5): 1677– 1692. doi: 10.1038/s41418-019-0452-0 31740789 PMC7206052 · DOI
  107. [116]Campisi D, Desrues L, Dembélé KP, et al. The core autophagy protein ATG9A controls dynamics of cell protrusions and directed migration. J Cell Biol. 2022 Mar 7; 221(3). doi: 10.1083/jcb.202106014 PMC8932524 35180289 · DOI
  108. [118]Hara T, Nakamura K, Matsui M, et al. Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature. 2006 Jun 15; 441(7095): 885– 889. doi: 10.1038/nature04724 16625204 · DOI · Paper page
  109. [119]Trentesaux C, Fraudeau M, Pitasi CL, et al. Essential role for autophagy protein ATG7 in the maintenance of intestinal stem cell integrity. Proc Natl Acad Sci USA. 2020 May 19; 117(20): 11136– 11146. doi: 10.1073/pnas.1917174117 32371487 PMC7245075 · DOI
  110. [120]Komatsu M, Waguri S, Chiba T, et al. Loss of autophagy in the central nervous system causes neurodegeneration in mice. Nature. 2006 Jun 15; 441(7095): 880– 884. doi: 10.1038/nature04723 16625205 · DOI · Paper page
  111. [121]Moreno-De-Luca A, Helmers SL, Mao H, et al. Adaptor protein complex-4 (AP-4) deficiency causes a novel autosomal recessive cerebral palsy syndrome with microcephaly and intellectual disability. J Med Genet. 2011 Feb; 48(2): 141– 144. doi: 10.1136/jmg.2010.082263 20972249 PMC3150730 · DOI
  112. [122]Aggarwal A, Reichert H, VijayRaghavan K. A locomotor assay reveals deficits in heterozygous Parkinson’s disease model and proprioceptive mutants in adult Drosophila. Proc Natl Acad Sci USA. 2019 Dec 3; 116(49): 24830– 24839. doi: 10.1073/pnas.1807456116 31748267 PMC6900508 · DOI
  113. [123]Cao M, Wu Y, Ashrafi G, et al. Parkinson sac domain mutation in synaptojanin 1 impairs clathrin uncoating at synapses and triggers dystrophic changes in dopaminergic axons. Neuron. 2017 Feb 22; 93(4): 882– 896 e5. doi: 10.1016/j.neuron.2017.01.019 28231468 PMC5340420 · DOI
  114. [125]Yi S, Wang L, Ho MS, et al. The autophagy protein Atg9 functions in glia and contributes to parkinsonian symptoms in a drosophila model of Parkinson’s disease. Neural Regen Res. 2024 May; 19(5): 1150– 1155. doi: 10.4103/1673-5374.382259 37862221 PMC10749615 · DOI
  115. [126]Bhukel A, Beuschel CB, Maglione M, et al. Autophagy within the mushroom body protects from synapse aging in a non-cell autonomous manner. Nat Commun. 2019 Mar 21; 10(1): 1318. doi: 10.1038/s41467-019-09262-2 30899013 PMC6428838 · DOI
  116. [127]Kakanj P, Bhide S, Moussian B, et al. Autophagy-mediated plasma membrane removal promotes the formation of epithelial syncytia. Embo J. 2022 Jun 14; 41(12): e109992. doi: 10.15252/embj.2021109992 35262206 PMC9194749 · DOI
  117. [128]Vale-Costa S, Etibor TA, Brás D, et al. ATG9A regulates the dissociation of recycling endosomes from microtubules to form liquid influenza a virus inclusions. PLOS Biol. 2023; 21(11): e3002290. doi: 10.1371/journal.pbio.3002290 37983294 PMC10695400 · DOI
  118. [129]Papin L, Lehmann M, Lagisquet J, et al. The autophagy nucleation factor ATG9 forms nanoclusters with the HIV-1 receptor DC-SIGN and regulates early antiviral autophagy in human dendritic cells. Int J Mol Sci. 2023 May 19; 24(10): 9008. doi: 10.3390/ijms24109008 37240354 PMC10219569 · DOI
  119. [130]Mailler E, Waheed AA, Park SY, et al. The autophagy protein ATG9A promotes HIV-1 infectivity. Retrovirology. 2019 Jul 3; 16(1): 18. doi: 10.1186/s12977-019-0480-3 31269971 PMC6607583 · DOI
  120. [131]Tang HW, Liao HM, Peng WH, et al. Atg9 interacts with dTRAF2/TRAF6 to regulate oxidative stress-induced JNK activation and autophagy induction. Dev Cell. 2013 Dec 9; 27(5): 489– 503. doi: 10.1016/j.devcel.2013.10.017 24268699 · DOI

Cited by

Sorted by citations

Authors
Choi, J., Jang, H., Xuan, Z., & Park, D.
Affiliations
  • The Catholic University of Korea
  • Catholic University of Korea (KR)
  • University of Maine
Corresponding author
Park, Daehun
ORCID
Venue
Autophagy
Publisher
Informa UK Limited
Published
2024-08-04
Volume
20
Issue
11
Pages
2373-2387
ISSN
  • 1554-8627 (ISSN-L)
  • 1554-8635
DOI
10.1080/15548627.2024.2384349
PMC
PMC11572220
OpenAlex
W4401345330
Cited by
28
References
11
Citations by year
2026: 11 · 2025: 17
FWCI
1.84
Type
journal article
Language
en
Open access
Licence
Locations
  • Autophagy (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
Brain Korea 21 Plus Program
Topics
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
Keywords
ATG9A, ATG9B, autophagosome formation, neurons, protein trafficking, synaptic vesicles, phosphatidylinositol 3-phosphate
MeSH terms
Autophagosomes, Autophagy-Related Proteins, Animals, Autophagy, Humans, Membrane Proteins, Neurons, Vesicular Transport Proteins

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