Einzeltreffer — DigiBib

Tripartite 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.

Titel:	TRIM27 is an autophagy substrate facilitating mitochondria clustering and mitophagy via phosphorylated TBK1.
Autor/in / Beteiligte Person:	Garcia-Garcia, J ; Berge, AKM ; Overå, KS ; Larsen, KB ; Bhujabal, Z ; Brech, A ; Abudu, YP ; Lamark, T ; Johansen, T ; Sjøttem, E
Link:	Zum Volltext
Zeitschrift:	The FEBS journal, Jg. 290 (2023-02-01), Heft 4, S. 1096-1116
Veröffentlichung:	Oxford, UK : Published by Blackwell Pub. on behalf of the Federation of European Biochemical Societies, c2005-, 2023
Medientyp:	academicJournal
ISSN:	1742-4658 (electronic)
DOI:	10.1111/febs.16628
Schlagwort:	Humans DNA-Binding Proteins metabolism HEK293 Cells Nuclear Proteins metabolism Protein Serine-Threonine Kinases genetics Protein Serine-Threonine Kinases metabolism Sequestosome-1 Protein metabolism Ubiquitin metabolism Autophagy physiology Mitochondria genetics Mitochondria metabolism Mitophagy physiology Ubiquitin-Protein Ligases metabolism Tripartite Motif Proteins metabolism
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, Non-U.S. Gov't Language: English [FEBS J] 2023 Feb; Vol. 290 (4), pp. 1096-1116. <i>Date of Electronic Publication: </i>2022 Sep 24. MeSH Terms: Autophagy* / physiology ; Mitochondria* / genetics ; Mitochondria* / metabolism ; Mitophagy* / physiology ; Ubiquitin-Protein Ligases* / metabolism ; Tripartite Motif Proteins* / metabolism ; Humans ; DNA-Binding Proteins / metabolism ; HEK293 Cells ; Nuclear Proteins / metabolism ; Protein Serine-Threonine Kinases / genetics ; Protein Serine-Threonine Kinases / metabolism ; Sequestosome-1 Protein / metabolism ; Ubiquitin / metabolism References: Swatek KN, Komander D. Ubiquitin modifications. Cell Res. 2016;26:399-422. ; Dikic I. Proteasomal and autophagic degradation systems. Annu Rev Biochem. 2017;86:193-224. ; Kwon YT, Ciechanover A. The ubiquitin code in the ubiquitin-proteasome system and autophagy. Trends Biochem Sci. 2017;42:873-86. ; Watanabe M, Hatakeyama S. TRIM proteins and diseases. J Biochem. 2017;161:135-44. ; Esposito D, Koliopoulos MG, Rittinger K. Structural determinants of TRIM protein function. Biochem Soc Trans. 2017;45:183-91. ; Di Rienzo M, Romagnoli A, Antonioli M, Piacentini M, Fimia GM. TRIM proteins in autophagy: selective sensors in cell damage and innate immune responses. Cell Death Differ. 2020;27:887-902. ; Mandell MA, Jain A, Arko-Mensah J, Chauhan S, Kimura T, Dinkins C, et al. TRIM proteins regulate autophagy and can target autophagic substrates by direct recognition. Dev Cell. 2014;30:394-409. ; Di Rienzo M, Antonioli M, Fusco C, Liu Y, Mari M, Orhon I, et al. Autophagy induction in atrophic muscle cells requires ULK1 activation by TRIM32 through unanchored K63-linked polyubiquitin chains. Sci Adv. 2019;5:eaau8857. ; Fusco C, Mandriani B, Di Rienzo M, Micale L, Malerba N, Cocciadiferro D, et al. TRIM50 regulates Beclin 1 proautophagic activity. Biochim Biophys Acta Mol Cell Res. 2018;1865:908-19. ; Mandell MA, Jain A, Kumar S, Castleman MJ, Anwar T, Eskelinen EL, et al. TRIM17 contributes to autophagy of midbodies while actively sparing other targets from degradation. J Cell Sci. 2016;129:3562-73. ; Kimura T, Jain A, Choi SW, Mandell MA, Schroder K, Johansen T, et al. TRIM-mediated precision autophagy targets cytoplasmic regulators of innate immunity. J Cell Biol. 2015;210:973-89. ; Sparrer KMJ, Gableske S, Zurenski MA, Parker ZM, Full F, Baumgart GJ, et al. TRIM23 mediates virus-induced autophagy via activation of TBK1. Nat Microbiol. 2017;2:1543-57. ; Overa KS, Garcia-Garcia J, Bhujabal Z, Jain A, Overvatn A, Larsen KB, et al. TRIM32, but not its muscular dystrophy-associated mutant, positively regulates and is targeted to autophagic degradation by p62/SQSTM1. J Cell Sci. 2019;132:jcs236596. ; Tomar D, Singh R, Singh AK, Pandya CD, Singh R. TRIM13 regulates ER stress induced autophagy and clonogenic ability of the cells. Biochim Biophys Acta. 2012;1823:316-26. ; Cao T, Borden KL, Freemont PS, Etkin LD. Involvement of the rfp tripartite motif in protein-protein interactions and subcellular distribution. J Cell Sci. 1997;110(Pt 14):1563-71. ; Tezel G, Nagasaka T, Iwahashi N, Asai N, Iwashita T, Sakata K, et al. Different nuclear/cytoplasmic distributions of RET finger protein in different cell types. Pathol Int. 1999;49:881-6. ; Ma Y, Wei Z, Bast RC Jr, Wang Z, Li Y, Gao M, et al. Downregulation of TRIM27 expression inhibits the proliferation of ovarian cancer cells in vitro and in vivo. Lab Invest. 2016;96:37-48. ; Zaman MM, Shinagawa T, Ishii S. Trim27-deficient mice are susceptible to streptozotocin-induced diabetes. FEBS Open Bio. 2013;4:60-4. ; Zheng Q, Hou J, Zhou Y, Yang Y, Xie B, Cao X. Siglec1 suppresses antiviral innate immune response by inducing TBK1 degradation via the ubiquitin ligase TRIM27. Cell Res. 2015;25:1121-36. ; Zhuang XJ, Tang WH, Feng X, Liu CY, Zhu JL, Yan J, et al. Trim27 interacts with Slx2, is associated with meiotic processes during spermatogenesis. Cell Cycle. 2016;15:2576-84. ; Zoumpoulidou G, Broceno C, Li H, Bird D, Thomas G, Mittnacht S. Role of the tripartite motif protein 27 in cancer development. J Natl Cancer Inst. 2012;104:941-52. ; Wang J, Teng JL, Zhao D, Ge P, Li B, Woo PC, et al. The ubiquitin ligase TRIM27 functions as a host restriction factor antagonized by mycobacterium tuberculosis PtpA during mycobacterial infection. Sci Rep. 2016;6:34827. ; Conwell SE, White AE, Harper JW, Knipe DM. Identification of TRIM27 as a novel degradation target of herpes simplex virus 1 ICP0. J Virol. 2015;89:220-9. ; Cai J, Chen HY, Peng SJ, Meng JL, Wang Y, Zhou Y, et al. USP7-TRIM27 axis negatively modulates antiviral type I IFN signaling. FASEB J. 2018;32(10):5238-49. ; Zaman MM, Nomura T, Takagi T, Okamura T, Jin W, Shinagawa T, et al. Ubiquitination-deubiquitination by the TRIM27-USP7 complex regulates tumor necrosis factor alpha-induced apoptosis. Mol Cell Biol. 2013;33:4971-84. ; Hao YH, Fountain MD Jr, Fon Tacer K, Xia F, Bi W, Kang SH, et al. USP7 acts as a molecular rheostat to promote WASH-dependent endosomal protein recycling and is mutated in a human neurodevelopmental disorder. Mol Cell. 2015;59:956-69. ; Iorio R, Celenza G, Petricca S. Mitophagy: molecular mechanisms, new concepts on parkin activation and the emerging role of AMPK/ULK1 Axis. Cell. 2021;11:30. ; Yamano K, Kikuchi R, Kojima W, Hayashida R, Koyano F, Kawawaki J, et al. Critical role of mitochondrial ubiquitination and the OPTN-ATG9A axis in mitophagy. J Cell Biol. 2020;219:e201912144. ; Kane LA, Lazarou M, Fogel AI, Li Y, Yamano K, Sarraf SA, et al. PINK1 phosphorylates ubiquitin to activate parkin E3 ubiquitin ligase activity. J Cell Biol. 2014;205:143-53. ; Kazlauskaite A, Kondapalli C, Gourlay R, Campbell DG, Ritorto MS, Hofmann K, et al. Parkin is activated by PINK1-dependent phosphorylation of ubiquitin at Ser65. Biochem J. 2014;460:127-39. ; Koyano F, Okatsu K, Kosako H, Tamura Y, Go E, Kimura M, et al. Ubiquitin is phosphorylated by PINK1 to activate parkin. Nature. 2014;510:162-6. ; Narendra DP, Jin SM, Tanaka A, Suen DF, Gautier CA, Shen J, et al. PINK1 is selectively stabilized on impaired mitochondria to activate parkin. PLoS Biol. 2010;8:e1000298. ; Lazarou M, Sliter DA, Kane LA, Sarraf SA, Wang C, Burman JL, et al. The ubiquitin kinase PINK1 recruits autophagy receptors to induce mitophagy. Nature. 2015;524:309-14. ; Heo JM, Ordureau A, Paulo JA, Rinehart J, Harper JW. The PINK1-PARKIN mitochondrial ubiquitylation pathway drives a program of OPTN/NDP52 recruitment and TBK1 activation to promote mitophagy. Mol Cell. 2015;60:7-20. ; Matsumoto G, Shimogori T, Hattori N, Nukina N. TBK1 controls autophagosomal engulfment of polyubiquitinated mitochondria through p62/SQSTM1 phosphorylation. Hum Mol Genet. 2015;24:4429-42. ; Richter B, Sliter DA, Herhaus L, Stolz A, Wang C, Beli P, et al. Phosphorylation of OPTN by TBK1 enhances its binding to Ub chains and promotes selective autophagy of damaged mitochondria. Proc Natl Acad Sci USA. 2016;113:4039-44. ; Vargas JNS, Wang C, Bunker E, Hao L, Maric D, Schiavo G, et al. Spatiotemporal control of ULK1 activation by NDP52 and TBK1 during selective autophagy. Mol Cell. 2019;74:347-362 e6. ; Onishi M, Yamano K, Sato M, Matsuda N, Okamoto K. Molecular mechanisms and physiological functions of mitophagy. EMBO J. 2021;40:e104705. ; Seabright AP, Fine NHF, Barlow JP, Lord SO, Musa I, Gray A, et al. AMPK activation induces mitophagy and promotes mitochondrial fission while activating TBK1 in a PINK1-parkin independent manner. FASEB J. 2020;34:6284-301. ; Nishida Y, Arakawa S, Fujitani K, Yamaguchi H, Mizuta T, Kanaseki T, et al. Discovery of Atg5/Atg7-independent alternative macroautophagy. Nature. 2009;461:654-8. ; Ohsumi Y. Historical landmarks of autophagy research. Cell Res. 2014;24:9-23. ; Orsi A, Razi M, Dooley HC, Robinson D, Weston AE, Collinson LM, et al. Dynamic and transient interactions of Atg9 with autophagosomes, but not membrane integration, are required for autophagy. Mol Biol Cell. 2012;23:1860-73. ; Ran FA, Hsu PD, Wright J, Agarwala V, Scott DA, Zhang F. Genome engineering using the CRISPR-Cas9 system. Nat Protoc. 2013;8:2281-308. ; Zurek B, Schoultz I, Neerincx A, Napolitano LM, Birkner K, Bennek E, et al. TRIM27 negatively regulates NOD2 by ubiquitination and proteasomal degradation. PLoS ONE. 2012;7:e41255. ; Harbers M, Nomura T, Ohno S, Ishii S. Intracellular localization of the ret finger protein depends on a functional nuclear export signal and protein kinase C activation. J Biol Chem. 2001;276:48596-607. ; Zhang Y, Feng Y, Ji D, Wang Q, Qian W, Wang S, et al. TRIM27 functions as an oncogene by activating epithelial-mesenchymal transition and p-AKT in colorectal cancer. Int J Oncol. 2018;53:620-32. ; Geisler S, Holmstrom KM, Skujat D, Fiesel FC, Rothfuss OC, Kahle PJ, et al. PINK1/parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1. Nat Cell Biol. 2010;12:119-31. ; Okatsu K, Saisho K, Shimanuki M, Nakada K, Shitara H, Sou YS, et al. p62/SQSTM1 cooperates with parkin for perinuclear clustering of depolarized mitochondria. Genes Cells. 2010;15:887-900. ; Zhong Z, Sanchez-Lopez E, Karin M. Autophagy, NLRP3 inflammasome and auto-inflammatory/immune diseases. Clin Exp Rheumatol. 2016;34:12-6. ; Nguyen TD, Shaid S, Vakhrusheva O, Koschade SE, Klann K, Tholken M, et al. Loss of the selective autophagy receptor p62 impairs murine myeloid leukemia progression and mitophagy. Blood. 2019;133:168-79. ; Moore AS, Holzbaur EL. Dynamic recruitment and activation of ALS-associated TBK1 with its target optineurin are required for efficient mitophagy. Proc Natl Acad Sci USA. 2016;113:E3349-58. ; Zachari M, Gudmundsson SR, Li Z, Manifava M, Cugliandolo F, Shah R, et al. Selective autophagy of mitochondria on a ubiquitin-endoplasmic-reticulum platform. Dev Cell. 2019;50:627-643 e5. ; Matsumoto G, Wada K, Okuno M, Kurosawa M, Nukina N. Serine 403 phosphorylation of p62/SQSTM1 regulates selective autophagic clearance of ubiquitinated proteins. Mol Cell. 2011;44:279-89. ; Pilli M, Arko-Mensah J, Ponpuak M, Roberts E, Master S, Mandell MA, et al. TBK-1 promotes autophagy-mediated antimicrobial defense by controlling autophagosome maturation. Immunity. 2012;37:223-34. ; Shu C, Sankaran B, Chaton CT, Herr AB, Mishra A, Peng J, et al. Structural insights into the functions of TBK1 in innate antimicrobial immunity. Structure. 2013;21:1137-48. ; Heo JM, Ordureau A, Swarup S, Paulo JA, Shen K, Sabatini DM, et al. RAB7A phosphorylation by TBK1 promotes mitophagy via the PINK-PARKIN pathway. Sci Adv. 2018;4:eaav0443. ; Bhujabal Z, Birgisdottir AB, Sjottem E, Brenne HB, Overvatn A, Habisov S, et al. FKBP8 recruits LC3A to mediate parkin-independent mitophagy. EMBO Rep. 2017;18:947-61. ; Sawa-Makarska J, Baumann V, Coudevylle N, von Bulow S, Nogellova V, Abert C, et al. Reconstitution of autophagosome nucleation defines Atg9 vesicles as seeds for membrane formation. Science. 2020;369:eaaz7714. ; Young AR, Chan EY, Hu XW, Kochl R, Crawshaw SG, High S, et al. Starvation and ULK1-dependent cycling of mammalian Atg9 between the TGN and endosomes. J Cell Sci. 2006;119:3888-900. ; Zhou C, Ma K, Gao R, Mu C, Chen L, Liu Q, et al. Regulation of mATG9 trafficking by Src- and ULK1-mediated phosphorylation in basal and starvation-induced autophagy. Cell Res. 2017;27:184-201. ; Koliopoulos MG, Esposito D, Christodoulou E, Taylor IA, Rittinger K. Functional role of TRIM E3 ligase oligomerization and regulation of catalytic activity. EMBO J. 2016;35:1204-18. ; Streich FC Jr, Ronchi VP, Connick JP, Haas AL. Tripartite motif ligases catalyze polyubiquitin chain formation through a cooperative allosteric mechanism. J Biol Chem. 2013;288:8209-21. ; Yudina Z, Roa A, Johnson R, Biris N, de Souza Aranha Vieira DA, Tsiperson V, et al. RING dimerization links higher-order assembly of TRIM5alpha to synthesis of K63-linked polyubiquitin. Cell Rep. 2015;12:788-97. ; Ravenhill BJ, Boyle KB, von Muhlinen N, Ellison CJ, Masson GR, Otten EG, et al. The cargo receptor NDP52 initiates selective autophagy by recruiting the ULK complex to cytosol-invading bacteria. Mol Cell. 2019;74:320-329 e6. ; Larabi A, Devos JM, Ng SL, Nanao MH, Round A, Maniatis T, et al. Crystal structure and mechanism of activation of TANK-binding kinase 1. Cell Rep. 2013;3:734-46. ; Gao B, Yu W, Lv P, Liang X, Sun S, Zhang Y. Parkin overexpression alleviates cardiac aging through facilitating K63-polyubiquitination of TBK1 to facilitate mitophagy. Biochim Biophys Acta Mol Basis Dis. 2021;1867:165997. ; Horio M, Kato T, Mii S, Enomoto A, Asai M, Asai N, et al. Expression of RET finger protein predicts chemoresistance in epithelial ovarian cancer. Cancer Med. 2012;1:218-29. ; Iwakoshi A, Murakumo Y, Kato T, Kitamura A, Mii S, Saito S, et al. RET finger protein expression is associated with prognosis in lung cancer with epidermal growth factor receptor mutations. Pathol Int. 2012;62:324-30. ; Jiang J, Xie C, Liu Y, Shi Q, Chen Y. Up-regulation of miR-383-5p suppresses proliferation and enhances chemosensitivity in ovarian cancer cells by targeting TRIM27. Biomed Pharmacother. 2019;109:595-601. ; Tezel GG, Uner A, Yildiz I, Guler G, Takahashi M. RET finger protein expression in invasive breast carcinoma: relationship between RFP and ErbB2 expression. Pathol Res Pract. 2009;205:403-8. ; Tsukamoto H, Kato T, Enomoto A, Nakamura N, Shimono Y, Jijiwa M, et al. Expression of ret finger protein correlates with outcomes in endometrial cancer. Cancer Sci. 2009;100:1895-901. ; Chang JY, Yi HS, Kim HW, Shong M. Dysregulation of mitophagy in carcinogenesis and tumor progression. Biochim Biophys Acta Bioenerg. 2017;1858:633-40. ; Vara-Perez M, Felipe-Abrio B, Agostinis P. Mitophagy in cancer: A tale of adaptation. Cell. 2019;8:493. ; Wang Y, Liu HH, Cao YT, Zhang LL, Huang F, Yi C. The role of mitochondrial dynamics and mitophagy in carcinogenesis, metastasis and therapy. Front Cell Dev Biol. 2020;8:413. ; Lamark T, Perander M, Outzen H, Kristiansen K, Overvatn A, Michaelsen E, et al. Interaction codes within the family of mammalian Phox and Bem1p domain-containing proteins. J Biol Chem. 2003;278:34568-81. Contributed Indexing: Keywords: SQSTM1/p62; TBK1; TRIM27; autophagy; mitophagy Substance Nomenclature: 0 (DNA-Binding Proteins) ; 0 (Nuclear Proteins) ; EC 2.7.11.1 (Protein Serine-Threonine Kinases) ; 0 (Sequestosome-1 Protein) ; EC 2.7.11.1 (TBK1 protein, human) ; 0 (TRIM27 protein, human) ; 0 (Ubiquitin) ; EC 2.3.2.27 (Ubiquitin-Protein Ligases) ; 0 (Tripartite Motif Proteins) Entry Date(s): Date Created: 20220916 Date Completed: 20230310 Latest Revision: 20230310 Update Code: 20240513

Klicken Sie ein Format an und speichern Sie dann die Daten oder geben Sie eine Empfänger-Adresse ein und lassen Sie sich per Email zusenden.

BibTeX Citavi, JabRef, u.a.
(Literaturverwaltung)

PDF kein Volltext!
(Merkzettel, Notizen)

RIS Endnote, Citavi u.a.
(Literaturverwaltung)

MODS
(XML zur Weiterverarbeitung)

oder

Wählen Sie das für Sie passende Zitationsformat und kopieren Sie es dann in die Zwischenablage, lassen es sich per Mail zusenden oder speichern es als PDF-Datei.

Gewünschter Zitations-Stil:

oder

Bitte prüfen Sie, ob die Zitation formal korrekt ist, bevor Sie sie in einer Arbeit verwenden. Benutzen Sie gegebenenfalls den "Exportieren"-Dialog, wenn Sie ein Literaturverwaltungsprogramm verwenden und die Zitat-Angaben selbst formatieren wollen.

TRIM27 is an autophagy substrate facilitating mitochondria clustering and mitophagy via phosphorylated TBK1.