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dc.contributor.authorNahse-Kumpf, Viola
dc.contributor.authorRaiborg, Camilla
dc.contributor.authorTan, Kia Wee
dc.contributor.authorMørk, Sissel
dc.contributor.authorTorgersen, Maria Lyngaas
dc.contributor.authorWenzel, Eva
dc.contributor.authorNager Grifo, Mireia
dc.contributor.authorSalo, Veijo T.
dc.contributor.authorJohansen, Terje
dc.contributor.authorIkonen, Elina
dc.contributor.authorSchink, Kay Oliver
dc.contributor.authorStenmark, Harald Alfred
dc.date.accessioned2023-08-08T07:37:13Z
dc.date.available2023-08-08T07:37:13Z
dc.date.issued2023-07-08
dc.description.abstractCellular 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.en_US
dc.identifier.citationNahse-Kumpf, Raiborg, Tan, Mørk, Torgersen, Wenzel, Nager Grifo, Salo, Johansen, Ikonen, Schink, Stenmark. ATPase activity of DFCP1 controls selective autophagy. Nature Communications. 2023;14(1)en_US
dc.identifier.cristinIDFRIDAID 2163792
dc.identifier.doi10.1038/s41467-023-39641-9
dc.identifier.issn2041-1723
dc.identifier.urihttps://hdl.handle.net/10037/29761
dc.language.isoengen_US
dc.publisherSpringer Natureen_US
dc.relation.journalNature Communications
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2023 The Author(s)en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0en_US
dc.rightsAttribution 4.0 International (CC BY 4.0)en_US
dc.titleATPase activity of DFCP1 controls selective autophagyen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US


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Attribution 4.0 International (CC BY 4.0)
Med mindre det står noe annet, er denne innførselens lisens beskrevet som Attribution 4.0 International (CC BY 4.0)