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Phosphorylation of OPTN by TBK1 enhances its binding to Ub chains and promotes selective autophagy of damaged mitochondria
Open accessAbstract
Significance: Selective autophagy of damaged mitochondria (mitophagy) requires protein kinases PINK1 and TBK1, ubiquitin ligase Parkin, and autophagy receptors such as OPTN, driving ubiquitin-labeled mitochondria into autophagosomes. Because all proteins have been genetically linked to either Parkinson’s disease (PINK1 and Parkin) or amyotrophic lateral sclerosis and frontotemporal lobar degeneration (TBK1 and OPTN), it is of great interest to understand their physiological functions. By utilizing quantitative proteomics we show that TBK1 phosphorylates four receptors on several autophagy-relevant sites. Constitutive interaction of TBK1 with OPTN and the ability of OPTN to bind to ubiquitin chains are essential for TBK1 recruitment and activation on mitochondria. TBK1-mediated phosphorylation of OPTN creates a signal amplification loop through combining recruitment and retention of OPTN/TBK1 on ubiquitinated mitochondria.
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“Through its phosphorylation of the autophagy receptors OPTN, SQSTM1, and CALCOCO2/NDP52 (calcium binding and coiled-coil domain 2) [58,59,194], TBK1 regulates several aspects of autophagy, including macroautophagy, xenophagy and mitophagy [59,90,148,194–196].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [194]
In the citing paper
“OPTN is an autophagy receptor that binds ubiquitinated cargo (via its UBAN domain) and LC3 (via its LIR domain) [194,254,255], although it can also act independently of target ubiquitination [254].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [194]
In the citing paper
“Mitochondrial protein ubiquitination promotes mitochondrial recruitment of autophagy regulators and receptors such as TBK1 and optineurin (Heo et al., 2015, Matsumoto et al., 2015, Richter et al., 2016).”
From A Cell-Based High-Throughput Screening Identified Two Compounds that Enhance PINK1-Parkin Signaling (2020) · cites this paper as Richter et al., 2016
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BackgroundMajor review: Molecular genetics of primary open-angle glaucoma
Liu, Y., & Allingham, R. R. (2017) · Experimental Eye Research · doi:10.1016/j.exer.2017.05.002 · Cited by 156
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Dynamic Regulation of Mitochondrial Import by the Ubiquitin System
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“Under normal circumstances, TBK1 responds to PINK1/Parkin-induced mitochondrial ubiquitination by phosphorylating several downstream autophagy receptors, including OPTN [77] and p62 [78].”
BackgroundMacroautophagy in CNS health and disease
Griffey, C. J., & Yamamoto, A. (2022) · Nature reviews. Neuroscience · doi:10.1038/s41583-022-00588-3 · Cited by 147
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“Similar to previous results, Parkin exhibited a trend for upregulation with ageing while optineurin, a receptor which is recruited to ubiquitin-tagged mitochondria subsequent to phosphorylation (Wong & Holzbaur, 2015; Richter et al. 2016), remained unchanged with age.”
ResultEmerging views of OPTN (optineurin) function in the autophagic process associated with disease
Qiu, Y., Wang, J., Li, H., Yang, B., Wang, J., He, Q., & Weng, Q. (2021) · Autophagy · doi:10.1080/15548627.2021.1908722 · Cited by 143
“autophagosomal membrane formation and promotes autophagosomal membrane recruitment to cargos by interacting with LC3 [10,53].”
BackgroundMitophagy in neurological disorders
Zhang, L., Dai, L., & Li, D. (2021) · Journal of Neuroinflammation · doi:10.1186/s12974-021-02334-5 · Cited by 143
“Nevertheless, the decreased efficiency caused by TBK1 or OPTN mutations may be sufficient to lead to enhanced neurodegeneration over time [41, 65, 97] (Fig.”
BackgroundVaites, L. P., Paulo, J. A., Huttlin, E. L., & Harper, J. W. (2018) · Molecular and Cellular Biology · doi:10.1128/mcb.00392-17 · Cited by 120
“translationally regulated by TBK1, thereby enhancing receptor association with UB chains on 400 damaged mitochondria and recruitment of ATG8-positive autophagic membranes (28-30, 48).”
BackgroundInfluentialVisualizing ubiquitination in mammalian cells
van Wijk, S. J. L., Fulda, S., Đikić, I., & Heilemann, M. (2019) · EMBO Reports · doi:10.15252/embr.201846520 · Cited by 135
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“Generally, PINK1 can phosphorylate ubiquitin chains on mitochondria and recruit autophagy receptors, such as NDP52 and OPTN, to induce mitophagy, which require PINK1 kinase activity and ubiquitin-binding domains of the receptors (Lazarou et al., 2015; Richter et al., 2016).”
Optineurin: A Coordinator of Membrane-Associated Cargo Trafficking and Autophagy
Ryan, T. A., & Tumbarello, D. A. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01024 · Cited by 140
“Phosphorylation of optineurin by TBK1 at Ser473 and Ser513 also enhances its binding affinity for polyubiquitin chains via the UBAN domain (51, 52).”
BackgroundInfluentialUnconventional initiation of PINK1/Parkin mitophagy by Optineurin
Nguyen, T. N., Sawa-Makarska, J. Z., Khuu, G., Lam, W. K., Adriaenssens, E., Fracchiolla, D., Shoebridge, S., Bernklau, D., Padman, B. S., Skulsuppaisarn, M., et al. (2023) · Molecular Cell · doi:10.1016/j.molcel.2023.04.021 · Cited by 138
Self-citationCommon Molecular Pathways in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia
Weishaupt, J. H., Hyman, T., & Đikić, I. (2016) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2016.07.005 · Cited by 130
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“OPTN involvement in autophagy depends on the activation of its LIR motif via the phosphorylation of a Ser residue preceding the core sequence, W/F/YXXL/I/V, by the TANK-binding kinase 1 (TBK1) [114,116].”
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Orchestration of selective autophagy by cargo receptors
Adriaenssens, E., Ferrari, L., & Martens, S. (2022) · Current Biology · doi:10.1016/j.cub.2022.11.002 · Cited by 122
Self-citationGenetic Convergence Brings Clarity to the Enigmatic Red Line in ALS
Cook, C. N., & Petrucelli, L. (2019) · Neuron · doi:10.1016/j.neuron.2019.02.032 · Cited by 126
Recruitment of TBK1 to cytosol‐invading Salmonella induces WIPI2‐dependent antibacterial autophagy
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“TBK1 also associates with optineurin and it has been reported to phosphorylate both optineurin and p62, thereby enhancing their affinity for LC3B and ubiquitin, respectively (Morton et al , 2008; Wild et al , 2011; Pilli et al , 2012; Heo et al , 2015; Richter et al , 2016).”
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“TBK1 also phosphorylates S473 in the UBAN domain of OPTN that enhances the functional efficacy of OPTN in selective autophagy [123,124,130].”
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InfluentialMolecular Mechanisms and Regulation of Mammalian Mitophagy
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“TBK1 was shown to phosphorylate OPTN at multiple sites in a PINK1- and PARKIN-dependent manner, leading to the increased affinity of OPTN for K63-Ub chains and ATG8 (yeast equivalent of LC3) proteins [90,91].”
BackgroundEmerging Principles of Selective ER Autophagy
Wilkinson, S. (2019) · Journal of Molecular Biology · doi:10.1016/j.jmb.2019.05.012 · Cited by 117
“Similarly, a feature of some other selective autophagy pathways is the activation of TBK1, which phosphorylates receptors within extended LIR motifs and ubiquitin-binding domains, in order to increase their GABARAP/LC3 or ubiquitin affinity, respectively [70,126].”
BackgroundSelective Autophagy of Mitochondria on a Ubiquitin-Endoplasmic-Reticulum Platform
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Resolving the Complexity of Ubiquitin Networks
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“Furthermore, TBK1 also phosphorylates other autophagy receptors, including OPTINEURIN (OPTN), NDP52 (CALCOCO2) and TAX1BP1 (Richter et al., 2016).”
BackgroundDysfunction of Optineurin in Amyotrophic Lateral Sclerosis and Glaucoma
Toth, R. P., & Atkin, J. D. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01017 · Cited by 114
“One major kinase that is capable of phosphorylating optineurin on at least nine serine and two threonine residues is TBK-1 (46).”
BackgroundLi, F., Xu, D., Wang, Y., Zhou, Z., Liu, J., Hu, S., Gong, Y., Yuan, J., & Pan, L. (2018) · Autophagy · doi:10.1080/15548627.2017.1391970 · Cited by 120
“involved selective autophagy has been proven to rely on the polyubiquitin binding ability of the OPTN UBAN domain.(21,22)”
BackgroundMethodInfluentialDiverse Functions of Autophagy in Liver Physiology and Liver Diseases
Ke, P. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20020300 · Cited by 117
Parkin inhibits BAK and BAX apoptotic function by distinct mechanisms during mitophagy
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“Adaptor proteins that bind to ubiquitin on the mitochondrial surface in turn recruit and extend the autophagosome around the damaged mito-chondrion (Wong & Holzbaur, 2014; Heo et al , 2015; Lazarou et al , 2015; Moore & Holzbaur, 2016; Richter et al , 2016).”
Mitophagy: A novel perspective for insighting into cancer and cancer treatment
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“tors to form signal amplification loops to regulate the selective autophagy process of damaged mitochondria.(32,33) TBK1 can also directly”
BackgroundDisease-modifying therapies in amyotrophic lateral sclerosis
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“These data point toward an increasingly complex network of interactions — involving feedback loops, signal amplification, and receptor plasticity — that ensure a robust autophagy response (Lazarou et al , 2015; Richter et al , 2016; Padman et al , 2019).”
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“Multiple components of the cGAS-STING activation cascade interact with autophagy relatedmolecules andpathways:TBK1hasbeennoted to activate mitophagy via phosphorylation of Calcium Binding And Coiled-Coil Domain 2 (NDP52), p62, TAX1BP1 and optineurin (69).”
BackgroundULK1 promotes mitophagy via phosphorylation and stabilization of BNIP3
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“A genetic variant in the BNIP3 promoter region (rs694539) correlates with an increased risk of developing NAFLD and certain cancers, perhaps due to its effect on mitophagy [71].”
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“PRKN subsequently ubiquitinates numerous OMM proteins and leads to the recruitment of different MAP1LC3/LC3 (microtubule-associated protein 1 light chain 3)-interacting region (LIR)-containing autophagy receptors, including OPTN (optineurin) and CALCOCO2/ NDP52 (calcium binding and coiled-coil domain 2) [19,20].”
BackgroundPINK1/Parkin Influences Cell Cycle by Sequestering TBK1 at Damaged Mitochondria, Inhibiting Mitosis
Sarraf, S. A., Sideris, D. P., Γιαγτζόγλου, Ν., Ni, L., Kankel, M. W., Sen, A., Bochicchio, L. A., Huang, C.-H., Nussenzweig, S. C., Worley, S. H., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.08.085 · Cited by 108
“TBK1 phosphorylates autophagy receptors at the mitochondria to promote binding between the developing autophagosome and damaged mitochondria (Heo et al., 2015; Lazarou et al., 2015; Moore and Holzbaur, 2016; Richter et al., 2016).”
BackgroundInfluentialSelf-citationUbiquitin and Receptor-Dependent Mitophagy Pathways and Their Implication in Neurodegeneration
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“During mitophagy, PINK1 and Parkin also trigger the translocation and activation of Tank Binding Kinase 1 (TBK1) to damaged mitochondria [44, 46, 47, 71].”
BackgroundDamaged mitochondria recruit the effector NEMO to activate NF-κB signaling
Harding, O. J., Holzer, E., Riley, J. F., Martens, S., & Holzbaur, E. L. F. (2023) · Molecular Cell · doi:10.1016/j.molcel.2023.08.005 · Cited by 105
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Zimmermann, M., & Reichert, A. S. (2017) · Biological Chemistry · doi:10.1515/hsz-2017-0206 · Cited by 104
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“As a result, phosphoubiquitination of OMM proteins by PINK1 and Parkin generates a specific signal and a platform for the recruitment of autophagy receptors for organelle degradation.”
BackgroundInfluentialKruppa, A. J., Kendrick‐Jones, J., & Buß, F. (2016) · Traffic · doi:10.1111/tra.12410 · Cited by 104
“TAX1BP1, OPTN and NDP52 are functionally redundant autophagy receptors and the latter two require Tank-binding kinase 1 (TBK1)-dependent phosphorylation to enhance their ability to bind ubiquitin chains (65,66), whereas NBR1 and p62 are dispensable for mitophagy (63,67).”
BackgroundRecruitment and Activation of the ULK1/Atg1 Kinase Complex in Selective Autophagy
Turco, E., Fracchiolla, D., & Martens, S. (2019) · Journal of Molecular Biology · doi:10.1016/j.jmb.2019.07.027 · Cited by 107
Self-citationPost-translational Modifications of Key Machinery in the Control of Mitophagy
Wang, L., Qi, H., Tang, Y., & Shen, H. (2019) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2019.08.002 · Cited by 102
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“Concomitant with receptor recruitment, the TBK1 kinase is activated and TBK1-mediated receptor phosphorylation promotes receptor ubiquitin chain binding and further TBK1 activation, thereby revealing another feed-forward mechanism (8, 34, 35).”
BackgroundATG4 family proteins drive phagophore growth independently of the LC3/GABARAP lipidation system
Nguyen, T. N., Padman, B. S., Zellner, S., Khuu, G., Uoselis, L., Lam, W. K., Skulsuppaisarn, M., Lindblom, R. S. J., Watts, E. M., Behrends, C., et al. (2021) · Molecular Cell · doi:10.1016/j.molcel.2021.03.001 · Cited by 106
Protein Homeostasis in Amyotrophic Lateral Sclerosis: Therapeutic Opportunities?
Webster, C. P., Smith, E. F., Shaw, P. J., & Vos, K. J. D. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00123 · Cited by 109
“Phosphorylation by TBK1 increases interaction of p62/sequestosome-1 and optineurin with LC3-II and/or ubiquitin chains, and increases autophagic clearance (Weidberg and Elazar, 2011; Wild et al., 2011; Matsumoto et al., 2015; Richter et al., 2016).”
BackgroundALS- and FTD-associated missense mutations in TBK1 differentially disrupt mitophagy
Harding, O. J., Evans, C. S., Ye, J., Cheung, J., Maniatis, T., & Holzbaur, E. L. F. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2025053118 · Cited by 99
“TBK1 recruitment is thought to be necessary for OPTN phosphorylation, which 483 enhances the affinity of OPTN for ubiquitin chains (7, 18) and is required for its interaction 484 with LC3 (10, 18, 27).”
InfluentialBansal, M., Moharir, S. C., Sailasree, P., Sirohi, K., Sudhakar, C., Sarathi, D. P., Lakshmi, B. J., Buono, M., Kumar, S., & Swarup, G. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m117.801944 · Cited by 99
Parkinson's: A Disease of Aberrant Vesicle Trafficking
Singh, P. K., & Muqit, M. M. K. (2020) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-100818-125512 · Cited by 97
“…been identified, including Optineurin (OPTN1), Tax-1 binding protein (TAX1BP1), p62/SQSTM1, and coiled-coil domain-containing protein 2 (CALCOCO2/NDP52), that are recruited to Ub chains assembled at the OMM and are required for mitophagy (Heo et al. 2015, Lazarou et al. 2015, Richter et al. 2016).”
BackgroundCellular Functions of Optineurin in Health and Disease
Slowicka, K., Vereecke, L., & Loo, G. (2016) · Trends in Immunology · doi:10.1016/j.it.2016.07.002 · Cited by 99
Mitchell, G., Cheng, M. I., Chen, C., Nguyen, B. N., Whiteley, A. T., Kianian, S., Cox, J. S., Green, D. R., McDonald, K. L., & Portnoy, D. A. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1716055115 · Cited by 98
“Typhimurium (11), this study confirmed that the initiation of a localized xenophagic response involved the protein kinase TBK1, which promotes macroautophagy by phosphorylating autophagy adaptors (11, 33, 34).”
BackgroundKinase regulation by liquid–liquid phase separation
López-Palacios, T. P., & Andersen, J. L. (2022) · Trends in Cell Biology · doi:10.1016/j.tcb.2022.11.009 · Cited by 95
Markovinović, A., Cimbro, R., Ljutić, T., Križ, J., Rogelj, B., & Munitić, I. (2017) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2017.04.005 · Cited by 95
Zhou, Z., Liu, J., Fu, T., Wu, P., Peng, C., Gong, X., Wang, Y., Zhang, M., Li, Y., Wang, Y., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-21874-1 · Cited by 98
Autophagy and Its Impact on Neurodegenerative Diseases: New Roles for TDP-43 and C9orf72
Budini, M., Buratti, E., Morselli, E., & Criollo, A. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00170 · Cited by 102
“Other studies have shown that TBK1 phosphorylates OPTN and p62/SQSTM1 to promote autophagy, and, when non-functional, TBK1 can impair autophagy and mitophagy, affecting neuronal homeostasis (Matsumoto et al., 2015; Richter et al., 2016).”
Glaucoma: from pathogenic mechanisms to retinal glial cell response to damage
Fernández‐Albarral, J. A., Ramirez, A. I., de Hoz, R., Matamoros, J. A., Salobrar‐García, E., Elvira‐Hurtado, L., López‐Cuenca, I., Sánchez-Puebla, L., Salazar, J. J., & Ramirez, J. M. (2024) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2024.1354569 · Cited by 105
Bloemberg, D., & Quadrilatero, J. (2019) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00261.2018 · Cited by 100
Scheffer, D. D. L., Garcia, A. A., Lee, L., Mochly‐Rosen, D., & Ferreira, J. C. B. (2022) · Antioxidants and Redox Signaling · doi:10.1089/ars.2021.0145 · Cited by 96
“4) (80, 162).”
Herhaus, L., Bhaskara, R. M., Lystad, A. H., Mato, U. G., Covarrubias‐Pinto, A., Bonn, F., Simonsen, A., Hummer, G., & Đikić, I. (2019) · EMBO Reports · doi:10.15252/embr.201948317 · Cited by 93
“23 Reggiori F (2017) Atg4 proteolytic activity can be inhibited by Atg1 phosphorylation. 778 Nature communications 8: 295 779 Satoo K, Noda NN, Kumeta H, Fujioka Y, Mizushima N, Ohsumi Y, Inagaki F (2009) The 780 structure of Atg4B-LC3 complex reveals the mechanism of LC3 processing and 781 delipidation during autopha…”
InfluentialSelf-citationMitophagy in the Pathogenesis of Liver Diseases
Ke, P. (2020) · Cells · doi:10.3390/cells9040831 · Cited by 91
Ling, Z., Liu, Y., Wang, Z., Zhang, Z., Chen, B., Yang, J., Zeng, B., Gao, Y., Jiang, C., Huang, Y., et al. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.833420 · Cited by 87
Protein trafficking at the crossroads to mitochondria
Wasilewski, M., Chojnacka, K., & Chacińska, A. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2016.10.019 · Cited by 95
“More recently, optineurin has been shown to be phosphorylated by Tank-binding kinase 1 (TBK1), which then promotes ubiquitin chain binding and efficient PINK1driven and Parkin-independent mitophagy [188,189].”
BackgroundBell, S. L., Lopez, K. L., Cox, J. S., Patrick, K. L., & Watson, R. O. (2021) · mBio · doi:10.1128/mbio.01871-20 · Cited by 92
“As a kinase, TBK1 can phosphorylate adapters like OPTN, NDP52, and p62 (Richter et al., 2016; Wild et al., 2011), and phosphorylation of OPTN by TBK1 can increase its affinity for ubiquitin.”
BackgroundMechanisms, pathophysiological roles and methods for analyzing mitophagy – recent insights
Williams, J. A. R., & Ding, W. (2017) · Biological Chemistry · doi:10.1515/hsz-2017-0228 · Cited by 92
“In addition, TBK1 phosphorylation of optineurin enhances its binding to phosphorylated Ser65 ubiquitin chains (Richter et al., 2016).”
BackgroundWu, Z., Wang, Y., Lim, J., Liu, B., Li, Y., Vartak, R. S., Stankiewicz, T. R., Montgomery, S. B., & Lu, B. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.05.007 · Cited by 87
Plant Selective Autophagy—Still an Uncharted Territory With a Lot of Hidden Gems
Stephani, M., & Dagdas, Y. (2019) · Journal of Molecular Biology · doi:10.1016/j.jmb.2019.06.028 · Cited by 86
Rab35 GTPase recruits NDP52 to autophagy targets
Minowa‐Nozawa, A., Nozawa, T., Okamoto‐Furuta, K., Kohda, H., & Nakagawa, I. (2017) · The EMBO Journal · doi:10.15252/embj.201796463 · Cited by 89
“Recently, TBK1 was reported to phosphorylate the coiled-coil and SKICH domains in NDP52 (Richter et al , 2016).”
Muench, N. A., Patel, S., Maes, M. E., Donahue, R., Ikeda, A., & Nickells, R. W. (2021) · Cells · doi:10.3390/cells10071593 · Cited by 93
“Of relevance to a discussion of the role of mitochondria in optic neuropathies, the activity of OPTN as a linker protein is enhanced by being phosphorylated by TANK-Binding Kinase 1 (TBK1), which increases both ubiquitinOPTN binding affinity [27] and OPTN-LC3 binding affinity [28].”
BackgroundMechanisms underlying ubiquitin-driven selective mitochondrial and bacterial autophagy
Goodall, E. A., Kraus, F., & Harper, J. W. (2022) · Molecular Cell · doi:10.1016/j.molcel.2022.03.012 · Cited by 86
Mitophagy in the pathogenesis and management of disease
Wang, Q., Sun, Y., Li, T. Y., & Auwerx, J. (2026) · Cell Research · doi:10.1038/s41422-025-01203-7 · Cited by 103
“74,75 Activated TBK1, in turn, phosphorylates NDP52 and OPTN at multiple sites, enhancing their binding to Ub chains 74,84 and the autophagy complex 78 to promote mitophagy.”
Weil, R., Laplantine, E., Curic, S., & Génin, P. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01243 · Cited by 83
Preserving Lysosomal Function in the Aging Brain: Insights from Neurodegeneration
Peng, W., Minakaki, G., Nguyen, M., & Krainc, D. (2019) · Neurotherapeutics · doi:10.1007/s13311-019-00742-3 · Cited by 79
ALS-associated missense and nonsense TBK1 mutations can both cause loss of kinase function
de Majo, M., Topp, S. D., Smith, B. N., Nishimura, A. L., Chen, H.-J., Gkazi, S. A., Miller, J. W., Wong, C. H., Vance, C. A., Baas, F., et al. (2018) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2018.06.015 · Cited by 86
“TBK1 is known to phosphorylate and regulate the activity of OPTN, a key receptor for polyubiquitinated proteins and mitochondria in autophagy pathways (Richter et al., 2016).”
BackgroundPDGF signaling inhibits mitophagy in glioblastoma stem cells through N-methyladenosine
Lv, D., Gimple, R. C., Zhong, C., Wu, Q., Yang, K., Prager, B. C., Godugu, B., Qiu, Z., Zhao, L., Zhang, G., et al. (2022) · Developmental Cell · doi:10.1016/j.devcel.2022.05.007 · Cited by 83
Mitophagy and Innate Immunity in Infection.
Cho, D., Kim, J. K., & Jo, E. (2020) · Europe PMC (PubMed Central) · doi:10.14348/molcells.2020.2329 · Cited by 85
“Importantly, the interaction of TBK1 with, and the phosphorylation of, OPTN is essential for promoting the binding of OPTN to Ub chains, which promotes mitophagy (Richter et al., 2016).”
BackgroundRawat, P., Teodorof‐Diedrich, C., & Spector, S. A. (2018) · Glia · doi:10.1002/glia.23568 · Cited by 81
“PINK1-Parkin-dependent TBK1 activation also plays a key role in recruitment of autophagy receptors OPTN and NDP52 on damaged mitochondria following mitochondrial depolarization to promote mitophagy (Heo, Ordureau, Paulo, Rinehart, & Harper, 2015; Richter et al., 2016).”
BackgroundThe role of autophagy in bone homeostasis
Guo, Y., Su, T., Yang, M., Li, C., Guo, Q., Xiao, Y., Huang, Y., Liu, Y., & Luo, X. (2021) · Journal of Cellular Physiology · doi:10.1002/jcp.30111 · Cited by 81
“Recently, a genome‐wide association approach found that variation in the Optn gene is a genetic risk factor for PDB. Optn has been characterized as an autophagy adapter protein that regulates selective autophagy of UB‐coated cytosolic proteins, organelles, and parasites such as Salmonella enteritidis.”
BackgroundInfluentialMaurel, C., Dangoumau, A., Marouillat, S., Brulard, C., Chami, A. A., Hergesheimer, R. C., Corcia, P., Blasco, H., Andres, C. R., & Vourc’h, P. (2018) · Molecular Neurobiology · doi:10.1007/s12035-017-0856-0 · Cited by 82
Impairment of Lysosome Function and Autophagy in Rare Neurodegenerative Diseases
Darios, F. D., & Stévanin, G. (2020) · Journal of Molecular Biology · doi:10.1016/j.jmb.2020.02.033 · Cited by 79
PINK1 in the limelight: multiple functions of an eclectic protein in human health and disease
Arena, G., & Valente, E. M. (2016) · The Journal of Pathology · doi:10.1002/path.4815 · Cited by 79
Metadata
- Authors
- Richter, B., Sliter, D. A., Herhaus, L., Stolz, A., Wang, C., Beli, P., Zaffagnini, G., Wild, P., Martens, S., Wagner, S. A., Youle, R. J., & Dikic, I.
- Affiliations
- Goethe University Frankfurt (DE)
- National Institutes of Health (US)
- Institute of Molecular Biology (DE)
- University of Vienna (AT)
- Institute of Biochemistry II, Goethe University School of Medicine, 60590 Frankfurt, Germany;
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2016-03-30
- Volume
- 113
- Issue
- 15
- Pages
- 4039-4044
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4839414
- OpenAlex
- W2323582440
- Cited by
- 755
- References
- 44
- Citations by year
- 2026: 64 · 2025: 69 · 2024: 71 · 2023: 56 · 2022: 80 · 2021: 95 · 2020: 82 · 2019: 74 · 2018: 77 · 2017: 60 · 2016: 27
- FWCI
- 74.58
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (DI 931/3-1)
- Cluster of Excellence (EXC115)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Keywords
- optineurin, TBK1, phosphorylation, selective autophagy, mitophagy, damaged mitochondria, ubiquitin chains, autophagy receptors, NDP52, TAX1BP1, p62, PINK1, Parkin, signal amplification
- MeSH terms
- Autophagy, HeLa Cells, Humans, Mitochondria, Phosphorylation, Protein Binding, Protein Serine-Threonine Kinases, Cell Cycle Proteins, Ubiquitin, Membrane Transport Proteins, Transcription Factor TFIIIA
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