Mammalian ATG8 proteins maintain autophagosomal membrane integrity through ESCRTs.
| Title: | Mammalian ATG8 proteins maintain autophagosomal membrane integrity through ESCRTs. |
|---|---|
| Authors: | Javed R; Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.; Autophagy, Inflammation and Metabolism Center of Biomedical Research Excellence, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.; Jain A; Faculty of Medicine, University of Oslo, Oslo, Norway.; Duque T; Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.; Autophagy, Inflammation and Metabolism Center of Biomedical Research Excellence, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.; Hendrix E; Department of Chemistry & Chemical Biology, The University of New Mexico, Albuquerque, NM, USA.; Paddar MA; Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.; Autophagy, Inflammation and Metabolism Center of Biomedical Research Excellence, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.; Khan S; Department of Physics and Astronomy, The University of New Mexico, Albuquerque, NM, USA.; Claude-Taupin A; Autophagy, Inflammation and Metabolism Center of Biomedical Research Excellence, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.; Jia J; Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.; Autophagy, Inflammation and Metabolism Center of Biomedical Research Excellence, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.; Allers L; Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.; Autophagy, Inflammation and Metabolism Center of Biomedical Research Excellence, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.; Wang F; Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.; Autophagy, Inflammation and Metabolism Center of Biomedical Research Excellence, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.; Mudd M; Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.; Autophagy, Inflammation and Metabolism Center of Biomedical Research Excellence, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.; Timmins G; Autophagy, Inflammation and Metabolism Center of Biomedical Research Excellence, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.; Lidke K; Department of Physics and Astronomy, The University of New Mexico, Albuquerque, NM, USA.; Rusten TE; Faculty of Medicine, University of Oslo, Oslo, Norway.; Akepati PR; Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of New Mexico, Albuquerque, NM, USA.; He Y; Department of Chemistry & Chemical Biology, The University of New Mexico, Albuquerque, NM, USA.; Reggiori F; Department of Biomedicine, Aarhus University, Aarhus, Denmark.; Aarhus Institute for Advanced Studies (AIAS), Aarhus University, Aarhus, Denmark.; Eskelinen EL; Institute of Biomedicine, University of Turku, Turku, Finland.; Deretic V; Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.; Autophagy, Inflammation and Metabolism Center of Biomedical Research Excellence, University of New Mexico Health Sciences Center, Albuquerque, NM, USA. |
| Source: | The EMBO journal [EMBO J] 2023 Jul 17; Vol. 42 (14), pp. e112845. Date of Electronic Publication: 2023 Jun 05. |
| Publication Type: | Journal Article; Research Support, N.I.H., Extramural |
| Language: | English |
| Journal Info: | Publisher: Nature Publishing Group Country of Publication: England NLM ID: 8208664 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1460-2075 (Electronic) Linking ISSN: 02614189 NLM ISO Abbreviation: EMBO J Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2024- : [London] : Nature Publishing Group; Original Publication: Eynsham, Oxford, England : Published for the European Molecular Biology Organization by IRL Press, [c1982- |
| MeSH Terms: | Microtubule-Associated Proteins*/genetics ; Microtubule-Associated Proteins*/metabolism ; Autophagy*; Autophagy-Related Protein 8 Family/genetics ; Autophagy-Related Protein 8 Family/metabolism ; Autophagosomes/metabolism ; Endosomal Sorting Complexes Required for Transport/metabolism ; Animals ; Humans ; Mammals |
| Abstract: | The canonical autophagy pathway in mammalian cells sequesters diverse cytoplasmic cargo within the double membrane autophagosomes that eventually convert into degradative compartments via fusion with endolysosomal intermediates. Here, we report that autophagosomal membranes show permeability in cells lacking principal ATG8 proteins (mATG8s) and are unable to mature into autolysosomes. Using a combination of methods including a novel in vitro assay to measure membrane sealing, we uncovered a previously unappreciated function of mATG8s to maintain autophagosomal membranes in a sealed state. The mATG8 proteins GABARAP and LC3A bind to key ESCRT-I components contributing, along with other ESCRTs, to the integrity and imperviousness of autophagic membranes. Autophagic organelles in cells lacking mATG8s are permeant, are arrested as amphisomes, and do not progress to functional autolysosomes. Thus, autophagosomal organelles need to be maintained in a sealed state in order to become lytic autolysosomes.; (© 2023 The Authors.) |
| References: | Cell Stress. 2021 Aug 12;5(9):128-142. (PMID: 34527862); Dev Cell. 2018 Apr 9;45(1):114-131.e8. (PMID: 29634932); Mol Biol Cell. 2002 Sep;13(9):3355-68. (PMID: 12221139); Biomed Opt Express. 2011 Apr 29;2(5):1377-93. (PMID: 21559149); EMBO Rep. 2018 Apr;19(4):. (PMID: 29437695); Nat Cell Biol. 2010 Sep;12(9):831-5. (PMID: 20811355); Dev Cell. 2020 Nov 9;55(3):289-297.e4. (PMID: 32916093); Nat Methods. 2010 May;7(5):373-5. (PMID: 20364146); BMC Bioinformatics. 2014 Dec 10;15:399. (PMID: 25491031); Autophagy. 2022 Feb;18(2):283-292. (PMID: 34036900); Nat Commun. 2018 Jul 20;9(1):2855. (PMID: 30030437); Cell. 2019 Jan 10;176(1-2):11-42. (PMID: 30633901); Nat Cell Biol. 2021 Aug;23(8):846-858. (PMID: 34257406); Autophagy. 2010 Aug;6(6):764-76. (PMID: 20639694); Sci Adv. 2021 Oct;7(40):eabj2485. (PMID: 34597140); Methods Mol Biol. 2008;445:11-28. (PMID: 18425441); Nature. 2021 Mar;591(7848):117-123. (PMID: 33442062); Cell. 2021 Nov 24;184(24):5950-5969.e22. (PMID: 34741801); J Cell Biol. 2005 May 9;169(3):425-34. (PMID: 15866887); Autophagy. 2020 Aug;16(8):1550-1552. (PMID: 32597364); Science. 2016 Nov 25;354(6315):1036-1041. (PMID: 27885029); Sci Rep. 2019 Jul 12;9(1):10147. (PMID: 31300716); Mol Cell. 2021 May 6;81(9):2013-2030.e9. (PMID: 33773106); Immunity. 2021 Mar 9;54(3):437-453. (PMID: 33691134); Phys Rev Lett. 2022 Dec 2;129(23):238101. (PMID: 36563190); Nat Struct Mol Biol. 2020 Jun;27(6):570-580. (PMID: 32424346); Nat Cell Biol. 2009 Dec;11(12):1433-7. (PMID: 19898463); Nat Cell Biol. 2014 Jun;16(6):495-501. (PMID: 24875736); J Cell Biol. 2022 Nov 7;221(11):. (PMID: 36179369); Annu Rev Cell Dev Biol. 2011;27:107-32. (PMID: 21801009); EMBO J. 2020 Dec 15;39(24):e104948. (PMID: 33226137); Proc Natl Acad Sci U S A. 2021 Apr 20;118(16):. (PMID: 33850023); Nat Cell Biol. 2021 May;23(5):450-456. (PMID: 33903736); Cell Host Microbe. 2014 Apr 9;15(4):403-11. (PMID: 24721569); J Cell Biol. 2008 Aug 25;182(4):685-701. (PMID: 18725538); Nat Struct Mol Biol. 2020 Dec;27(12):1194-1201. (PMID: 33106659); Elife. 2014 Nov 28;3:e04135. (PMID: 25432021); N Engl J Med. 2020 Oct 15;383(16):1564-1576. (PMID: 33053285); Nature. 2000 Nov 23;408(6811):488-92. (PMID: 11100732); Mol Biol Cell. 2004 Sep;15(9):4337-46. (PMID: 15240819); J Cell Biol. 2011 Jan 10;192(1):17-27. (PMID: 21220506); Cell Metab. 2019 Apr 2;29(4):803-826. (PMID: 30943392); Nat Commun. 2019 Nov 7;10(1):5058. (PMID: 31699981); Sci Rep. 2021 Dec 8;11(1):23672. (PMID: 34880301); J Cell Biol. 2019 Jun 3;218(6):1787-1798. (PMID: 30952800); EMBO J. 2016 Sep 1;35(17):1853-67. (PMID: 27340123); Nat Cell Biol. 2010 Aug;12(8):747-57. (PMID: 20639872); J Cell Biol. 2022 Jul 4;221(7):. (PMID: 35699692); Cell. 2011 Jul 22;146(2):303-17. (PMID: 21784250); Cell. 2019 Jun 13;177(7):1682-1699. (PMID: 31199916); Nature. 1998 Sep 24;395(6700):395-8. (PMID: 9759731); J Cell Sci. 2012 Mar 15;125(Pt 6):1488-99. (PMID: 22275429); Bioinformatics. 2006 Nov 1;22(21):2695-6. (PMID: 16940322); EMBO J. 2023 Jul 17;42(14):e112845. (PMID: 37272163); Nat Struct Mol Biol. 2020 Dec;27(12):1185-1193. (PMID: 33106658); J Cell Biol. 2013 Jul 22;202(2):331-49. (PMID: 23878278); Nature. 2008 Feb 28;451(7182):1069-75. (PMID: 18305538); Mol Biol Cell. 2008 Nov;19(11):4762-75. (PMID: 18768753); Nature. 2007 Dec 20;450(7173):1253-7. (PMID: 18097414); Elife. 2022 Aug 08;11:. (PMID: 35938926); PLoS Biol. 2019 Apr 1;17(4):e2007044. (PMID: 30933966); J Cell Biol. 2008 Dec 1;183(5):795-803. (PMID: 19029340); Dev Cell. 2011 Apr 19;20(4):444-54. (PMID: 21497758); J Cell Biol. 1997 Jan 13;136(1):61-70. (PMID: 9008703); Nucleic Acids Res. 2010 Jan;38(Database issue):D142-8. (PMID: 19843607); Curr Opin Cell Biol. 2020 Apr;63:1-10. (PMID: 31901645); EMBO J. 2010 Jun 2;29(11):1792-802. (PMID: 20418806); Dev Cell. 2019 Apr 8;49(1):130-144.e6. (PMID: 30827897); J Cell Biol. 2016 Dec 19;215(6):857-874. (PMID: 27864321); Annu Rev Cell Dev Biol. 2019 Oct 6;35:453-475. (PMID: 31283377); Biochem Biophys Res Commun. 1988 Feb 29;151(1):40-7. (PMID: 3126737); Elife. 2013 Aug 06;2:e00947. (PMID: 23930225); EMBO J. 2021 Oct 1;40(19):e108863. (PMID: 34459017); J Cell Biol. 2008 May 5;181(3):497-510. (PMID: 18443221); Dev Cell. 2017 Dec 18;43(6):716-730.e7. (PMID: 29257951); Nat Cell Biol. 2020 Aug;22(8):973-985. (PMID: 32753672); Mol Biol Cell. 2008 Nov;19(11):4651-9. (PMID: 18768752); PLoS Genet. 2022 Jun 30;18(6):e1010264. (PMID: 35771772); EMBO J. 2015 Oct 1;34(19):2398-407. (PMID: 26311197); Mol Cell. 2018 Apr 5;70(1):120-135.e8. (PMID: 29625033); J Cell Biol. 2018 Mar 5;217(3):997-1013. (PMID: 29420192); J Biol Chem. 2003 Aug 1;278(31):29278-87. (PMID: 12740394); EMBO J. 2021 Apr 1;40(7):e106922. (PMID: 33644904); Nat Cell Biol. 2020 Feb;22(2):187-199. (PMID: 31932738); J Cell Biol. 2012 May 28;197(5):659-75. (PMID: 22613832); EMBO J. 2019 Nov 15;38(22):e101994. (PMID: 31625181); Science. 2019 Aug 16;365(6454):. (PMID: 31416937); Nat Struct Mol Biol. 2021 Jul;28(7):583-593. (PMID: 34239122); EMBO J. 2017 Jun 14;36(12):1719-1735. (PMID: 28495679); Trends Biochem Sci. 2017 Jan;42(1):42-56. (PMID: 27669649); Autophagy. 2020 May;16(5):826-841. (PMID: 31366282); EMBO J. 2002 May 15;21(10):2397-406. (PMID: 12006492); EMBO Rep. 2017 Sep;18(9):1586-1603. (PMID: 28754694); EMBO Rep. 2017 Aug;18(8):1382-1396. (PMID: 28655748); J Cell Biol. 2019 Mar 4;218(3):757-770. (PMID: 30578282); J Cell Biol. 2018 Aug 6;217(8):2633-2645. (PMID: 29789439); J Biol Chem. 1998 Aug 21;273(34):21883-92. (PMID: 9705327); Autophagy. 2015 Nov 2;11(11):2134-2137. (PMID: 26466816); Nat Commun. 2020 Sep 17;11(1):4684. (PMID: 32943635); Annu Rev Cell Dev Biol. 2021 Oct 6;37:143-169. (PMID: 34152791); EMBO J. 2000 Nov 1;19(21):5720-8. (PMID: 11060023); Mol Cell. 2015 Jan 8;57(1):39-54. (PMID: 25498145); J Cell Biol. 2019 Oct 7;218(10):3336-3354. (PMID: 31519728); Cell Rep. 2021 Oct 26;37(4):109899. (PMID: 34706226); Dev Cell. 2020 Jan 6;52(1):69-87.e8. (PMID: 31813797); Cell. 2013 Sep 12;154(6):1285-99. (PMID: 24034251); Nat Cell Biol. 2020 Oct;22(10):1252-1263. (PMID: 32989250); Genomics. 2001 Jun 15;74(3):408-13. (PMID: 11414770) |
| Grant Information: | P20 GM121176 United States GM NIGMS NIH HHS; R37 AI042999 United States AI NIAID NIH HHS; R01 AI111935 United States AI NIAID NIH HHS |
| Contributed Indexing: | Keywords: ATG8; ESCRT; LC3; amphisome; autophagy |
| Substance Nomenclature: | 0 (Autophagy-Related Protein 8 Family); 0 (Microtubule-Associated Proteins); 0 (Endosomal Sorting Complexes Required for Transport) |
| Entry Date(s): | Date Created: 20230605 Date Completed: 20230718 Latest Revision: 20240606 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC10350836 |
| DOI: | 10.15252/embj.2022112845 |
| PMID: | 37272163 |
| Database: | MEDLINE |
Journal Article; Research Support, N.I.H., Extramural