ATPase activity of DFCP1 controls selective autophagy.
| Title: | ATPase activity of DFCP1 controls selective autophagy. |
|---|---|
| Authors: | Nähse V; Centre for Cancer Cell Reprogramming, Faculty of Medicine, University of Oslo, Montebello, N-0379, Oslo, Norway. Viola.Naehse@rr-research.no.; Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Montebello, 0379, Oslo, Norway. Viola.Naehse@rr-research.no.; Department of Anatomy and Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland. Viola.Naehse@rr-research.no.; Raiborg C; Centre for Cancer Cell Reprogramming, Faculty of Medicine, University of Oslo, Montebello, N-0379, Oslo, Norway.; Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Montebello, 0379, Oslo, Norway.; Tan KW; Centre for Cancer Cell Reprogramming, Faculty of Medicine, University of Oslo, Montebello, N-0379, Oslo, Norway.; Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Montebello, 0379, Oslo, Norway.; Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.; Mørk S; Centre for Cancer Cell Reprogramming, Faculty of Medicine, University of Oslo, Montebello, N-0379, Oslo, Norway.; Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Montebello, 0379, Oslo, Norway.; Torgersen ML; Centre for Cancer Cell Reprogramming, Faculty of Medicine, University of Oslo, Montebello, N-0379, Oslo, Norway.; Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Montebello, 0379, Oslo, Norway.; Wenzel EM; Centre for Cancer Cell Reprogramming, Faculty of Medicine, University of Oslo, Montebello, N-0379, Oslo, Norway.; Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Montebello, 0379, Oslo, Norway.; Nager M; Autophagy Research Group, Department of Medical Biology, University of Tromsø, The Arctic University of Norway, Tromsø, Norway.; Salo VT; Department of Anatomy and Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.; Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany.; Johansen T; Ikonen E; Department of Anatomy and Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.; Schink KO; Centre for Cancer Cell Reprogramming, Faculty of Medicine, University of Oslo, Montebello, N-0379, Oslo, Norway. k.o.schink@medisin.uio.no.; Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Montebello, 0379, Oslo, Norway. k.o.schink@medisin.uio.no.; Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, PO Box 1112, Blindern, 0317, Oslo, Norway. k.o.schink@medisin.uio.no.; Stenmark H; Centre for Cancer Cell Reprogramming, Faculty of Medicine, University of Oslo, Montebello, N-0379, Oslo, Norway. h.a.stenmark@medisin.uio.no.; Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Montebello, 0379, Oslo, Norway. h.a.stenmark@medisin.uio.no. |
| Source: | Nature communications [Nat Commun] 2023 Jul 08; Vol. 14 (1), pp. 4051. Date of Electronic Publication: 2023 Jul 08. |
| Publication Type: | Journal Article; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [London] : Nature Pub. Group |
| MeSH Terms: | Autophagy*/genetics ; Macroautophagy*; Endoplasmic Reticulum/metabolism ; Adenosine Triphosphatases/genetics ; Adenosine Triphosphatases/metabolism ; Adenosine Triphosphate/metabolism |
| Abstract: | Cellular homeostasis is governed by removal of damaged organelles and protein aggregates by selective autophagy mediated by cargo adaptors such as p62/SQSTM1. Autophagosomes can assemble in specialized cup-shaped regions of the endoplasmic reticulum (ER) known as omegasomes, which are characterized by the presence of the ER protein DFCP1/ZFYVE1. The function of DFCP1 is unknown, as are the mechanisms of omegasome formation and constriction. Here, we demonstrate that DFCP1 is an ATPase that is activated by membrane binding and dimerizes in an ATP-dependent fashion. Whereas depletion of DFCP1 has a minor effect on bulk autophagic flux, DFCP1 is required to maintain the autophagic flux of p62 under both fed and starved conditions, and this is dependent on its ability to bind and hydrolyse ATP. While DFCP1 mutants defective in ATP binding or hydrolysis localize to forming omegasomes, these omegasomes fail to constrict properly in a size-dependent manner. Consequently, the release of nascent autophagosomes from large omegasomes is markedly delayed. While knockout of DFCP1 does not affect bulk autophagy, it inhibits selective autophagy, including aggrephagy, mitophagy and micronucleophagy. We conclude that DFCP1 mediates ATPase-driven constriction of large omegasomes to release autophagosomes for selective autophagy.; (© 2023. The Author(s).) |
| References: | Nat Protoc. 2015 Jun;10(6):845-58. (PMID: 25950237); Genome Biol. 2015 Nov 10;16:231. (PMID: 26553065); Proc Natl Acad Sci U S A. 2011 Sep 27;108(39):16283-8. (PMID: 21930898); J Cell Sci. 2015 Jan 15;128(2):207-17. (PMID: 25568150); Curr Biol. 2017 Jul 24;27(14):2123-2136.e7. (PMID: 28712572); J Cell Biol. 2021 Aug 2;220(8):. (PMID: 34037656); Chem Biol. 2011 Aug 26;18(8):1042-52. (PMID: 21867919); Nat Commun. 2019 Sep 13;10(1):4176. (PMID: 31519908); Nature. 2007 Oct 18;449(7164):923-7. (PMID: 17914359); Cell. 2016 Feb 25;164(5):896-910. (PMID: 26919428); Nat Cell Biol. 2018 Feb;20(2):135-143. (PMID: 29230017); Cell Res. 2014 Jan;24(1):9-23. (PMID: 24366340); Autophagy. 2010 Aug;6(6):764-76. (PMID: 20639694); EMBO J. 1982;1(8):945-51. (PMID: 6329717); J Biol Chem. 1993 Aug 15;268(23):17240-6. (PMID: 8349610); J Comput Chem. 2004 Oct;25(13):1605-12. (PMID: 15264254); Nat Cell Biol. 2009 Dec;11(12):1433-7. (PMID: 19898463); Mol Cell. 2014 Jul 17;55(2):238-52. (PMID: 24954904); BMC Biol. 2016 Mar 02;14:14. (PMID: 26934976); Autophagy. 2009 Nov;5(8):1180-5. (PMID: 19855179); J Cell Biol. 2010 Aug 23;190(4):511-21. (PMID: 20713597); J Cell Biol. 2008 Aug 25;182(4):685-701. (PMID: 18725538); J Am Chem Soc. 2009 Aug 5;131(30):10356-7. (PMID: 19722611); Cells. 2021 Dec 06;10(12):. (PMID: 34943939); J Cell Biol. 2011 Jan 10;192(1):17-27. (PMID: 21220506); Methods Mol Biol. 2022;2445:99-115. (PMID: 34972988); EMBO J. 2016 Nov 2;35(21):2270-2284. (PMID: 27670760); Cell Rep. 2021 Nov 23;37(8):110049. (PMID: 34788596); Nat Methods. 2012 Jun 28;9(7):676-82. (PMID: 22743772); Nat Rev Mol Cell Biol. 2012 Jan 11;13(2):75-88. (PMID: 22233676); Biopolymers. 2016 Aug;105(8):580-93. (PMID: 27062152); Nature. 2021 Aug;596(7873):583-589. (PMID: 34265844); PLoS One. 2009 Aug 06;4(8):e6529. (PMID: 19657394); Mol Biol Cell. 2001 Sep;12(9):2578-89. (PMID: 11553700); J Cell Sci. 2013 Nov 15;126(Pt 22):5224-38. (PMID: 24013547); Nat Commun. 2018 Dec 5;9(1):5187. (PMID: 30518883); EMBO J. 2000 Sep 1;19(17):4555-64. (PMID: 10970849); J Biol Chem. 2007 Aug 17;282(33):24131-45. (PMID: 17580304); Nature. 2013 Mar 21;495(7441):389-93. (PMID: 23455425); Autophagy. 2010 May;6(4):506-22. (PMID: 20505359); J Cell Biol. 2005 Nov 21;171(4):603-14. (PMID: 16286508); Autophagy. 2013 Oct;9(10):1491-9. (PMID: 23884233); Mol Cell. 2017 Sep 21;67(6):974-989.e6. (PMID: 28890335); Protein Expr Purif. 2005 May;41(1):207-34. (PMID: 15915565); EMBO Rep. 2013 Dec;14(12):1127-35. (PMID: 24176932); Curr Genet. 2020 Aug;66(4):683-687. (PMID: 32077993) |
| Substance Nomenclature: | EC 3.6.1.- (Adenosine Triphosphatases); 8L70Q75FXE (Adenosine Triphosphate) |
| Entry Date(s): | Date Created: 20230708 Date Completed: 20230710 Latest Revision: 20231117 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC10329651 |
| DOI: | 10.1038/s41467-023-39641-9 |
| PMID: | 37422481 |
| Database: | MEDLINE |
Journal Article; Research Support, Non-U.S. Gov't