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dc.contributor.authorGarcia, Juncal Garcia
dc.contributor.authorBerge, Anne Kristin McLaren
dc.contributor.authorOverå, Katrine Stange
dc.contributor.authorLarsen, Kenneth Bowitz
dc.contributor.authorBhujabal, Zambarlal Babanrao
dc.contributor.authorBrech, Andreas
dc.contributor.authorAbudu, Yakubu Princely
dc.contributor.authorLamark, Trond
dc.contributor.authorJohansen, Terje
dc.contributor.authorSjøttem, Eva
dc.date.accessioned2023-01-06T10:04:25Z
dc.date.available2023-01-06T10:04:25Z
dc.date.issued2022-09-16
dc.description.abstractTripartite motif-containing protein 27 (TRIM27/also called RFP) is a multifunctional ubiquitin E3 ligase involved in numerous cellular functions, such as proliferation, apoptosis, regulation of the NF-kB pathway, endosomal recycling and the innate immune response. TRIM27 interacts directly with TANK-binding kinase 1 (TBK1) and regulates its stability. TBK1 in complex with autophagy receptors is recruited to ubiquitin chains assembled on the mitochondrial outer membrane promoting mitophagy. Here, we identify TRIM27 as an autophagy substrate, depending on ATG7, ATG9 and autophagy receptors for its lysosomal degradation. We show that TRIM27 forms ubiquitylated cytoplasmic bodies that co-localize with autophagy receptors. Surprisingly, we observed that induced expression of EGFP-TRIM27 in HEK293 FlpIn TRIM27 knockout cells mediates mitochondrial clustering. TRIM27 interacts with autophagy receptor SQSTM1/p62, and the TRIM27-mediated mitochondrial clustering is facilitated by SQSTM/p62. We show that phosphorylated TBK1 is recruited to the clustered mitochondria. Moreover, induced mitophagy activity is reduced in HEK293 FlpIn TRIM27 knockout cells, while re-introduction of EGFP-TRIM27 completely restores the mitophagy activity. Inhibition of TBK1 reduces mitophagy in HEK293 FlpIn cells and in the reconstituted EGFP-TRIM27-expressing cells, but not in HEK293 FlpIn TRIM27 knockout cells. Altogether, these data reveal novel roles for TRIM27 in mitophagy, facilitating mitochondrial clustering via SQSTM1/p62 and mitophagy via stabilization of phosphorylated TBK1 on mitochondria.en_US
dc.identifier.citationGarcia, Berge AKM, Overå, Larsen, Bhujabal, Brech, Abudu, Lamark, Johansen, Sjøttem. TRIM27 is an autophagy substrate facilitating mitochondria clustering and mitophagy via phosphorylated TBK1. The FEBS Journal. 2022en_US
dc.identifier.cristinIDFRIDAID 2060608
dc.identifier.doi10.1111/febs.16628
dc.identifier.issn1742-464X
dc.identifier.issn1742-4658
dc.identifier.urihttps://hdl.handle.net/10037/28048
dc.language.isoengen_US
dc.publisherWileyen_US
dc.relation.journalThe FEBS Journal
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2022 The Author(s)en_US
dc.rights.urihttps://creativecommons.org/licenses/by-nc/4.0en_US
dc.rightsAttribution-NonCommercial 4.0 International (CC BY-NC 4.0)en_US
dc.titleTRIM27 is an autophagy substrate facilitating mitochondria clustering and mitophagy via phosphorylated TBK1en_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)
Except where otherwise noted, this item's license is described as Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)