The DOI matches its Crossref record; 54 of the 54 references it cites were found in a registry or an index.
Ubiquitin-independent function of optineurin in autophagic clearance of protein aggregates
Open accessAbstract
Summary: Aggregation of misfolded proteins and the associated loss of neurons are considered a hallmark of numerous neurodegenerative diseases. Optineurin is present in protein inclusions observed in various neurodegenerative diseases including amyotrophic lateral sclerosis (ALS), Huntington's disease, Alzheimer's disease, Parkinson's disease, Creutzfeld-Jacob disease and Pick's disease. Optineurin deletion mutations have also been described in ALS patients. However, the role of optineurin in mechanisms of protein aggregation remains unclear. In this report, we demonstrate that optineurin recognizes various protein aggregates via its C-terminal coiled-coil domain in a ubiquitin-independent manner. We also show that optineurin depletion significantly increases protein aggregation in HeLa cells and that morpholino-silencing of the optineurin ortholog in zebrafish causes the motor axonopathy phenotype similar to a zebrafish model of ALS. A more severe phenotype is observed when optineurin is depleted in zebrafish carrying ALS mutations. Furthermore, TANK1 binding kinase 1 (TBK1) is colocalized with optineurin on protein aggregates and is important in clearance of protein aggregates through the autophagy-lysosome pathway. TBK1 phosphorylates optineurin at serine 177 and regulates its ability to interact with autophagy modifiers. This study provides evidence for a ubiquitin-independent function of optineurin in autophagic clearance of protein aggregates as well as additional relevance for TBK1 as an upstream regulator of the autophagic pathway.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
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 [254]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
The zebrafish book : a guide for the laboratory use of zebrafish (Danio rerio)
Westerfield, M. (1995) · Medical Entomology and Zoology · Cited by 6,813
Pankiv, S., Clausen, T. H., Lamark, T., Brech, A., Bruun, J.-A., Outzen, H., Øvervatn, A., Bjørkøy, G., & Johansen, T. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m702824200 · Cited by 4,578
Motor Neuron Degeneration in Mice that Express a Human Cu,Zn Superoxide Dismutase Mutation
Gurney, M. E., Pu, H., Chiu, A. Y., Dal Canto, M. C., Polchow, C. Y., Alexander, D. D., Caliendo, J., Hentati, A., Kwon, Y. W., Deng, H.-X., et al. (1994) · Science · doi:10.1126/science.8209258 · Cited by 4,143
Haine, M. M.-L., & Meeùs, N. (1986) · Cited by 3,464
The Role of Atg Proteins in Autophagosome Formation
Mizushima, N., Yoshimori, T., & Ohsumi, Y. (2011) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-092910-154005 · Cited by 2,978
Network organization of the human autophagy system
Behrends, C., Sowa, M. E., Gygi, S. P., & Harper, J. W. (2010) · Nature · doi:10.1038/nature09204 · Cited by 1,554
Nix is a selective autophagy receptor for mitochondrial clearance
Novak, I., Kirkin, V., McEwan, D. G., Zhang, J., Wild, P., Rozenknop, A., Rogov, V., Löhr, F., Popovic, D., Occhipinti, A., et al. (2010) · The EMBO Reports · doi:10.1038/embor.2009.256 · Cited by 1,309 · cited 2×
“, 2010), defective mitochondria (Novak et al., 2010) and bacteria Salmonella enterica (Thurston”
BackgroundPhosphorylation of the Autophagy Receptor Optineurin Restricts Salmonella Growth
Wild, P., Farhan, H., McEwan, D. G., Wagner, S., Rogov, V. V., Brady, N. R., Richter, B., Korac, J., Waidmann, O., Choudhary, C., et al. (2011) · Science · doi:10.1126/science.1205405 · Cited by 1,298
A Role for Ubiquitin in Selective Autophagy
Kirkin, V., McEwan, D. G., Novak, I., & Đikić, I. (2009) · Molecular Cell · doi:10.1016/j.molcel.2009.04.026 · Cited by 1,268
Mutations of optineurin in amyotrophic lateral sclerosis
Maruyama, H., Morino, H., Ito, H., Izumi, Y., Kato, H., Watanabe, Y., Kinoshita, Y., Kamada, M., Nodera, H., Suzuki, H., et al. (2010) · Nature · doi:10.1038/nature08971 · Cited by 1,265
Flagged first, then by citations
Cited by
Sorted by citations
Items 301–337 of 337
Li, Y. (2014) · Deep Blue (University of Michigan)
Autophagy and antigen processing : strategies to enhance T cell recognition of cancer cells
Williams, L. (2014) · University of Birmingham Institutional Research Archive (University of Birmingham)
Sanford, Z. (2015) · Marshall Journal of Medicine · doi:10.18590/mjm.2015.vol1.iss1.3
Mammalian Expression and Biophysical Examination of Human Wild Type Optineurin Protein
Ying, H., Shen, X., Wang, M., & Yue, J. (2015)
Gao, J. (2013) · HamaMed-Repository (Hamamatsu University School of Medicine)
Physiological Role of Autophagy and Implications in Disease
Karanasios, E., & Ktistakis, N. T. (2016) · Springer eBooks · doi:10.1007/978-3-319-33145-4_5
Tan, S. (2017) · DR-NTU (Nanyang Technological University) · doi:10.32657/10356/72655
Identification of the Stress Which Causes Optineurin Aggregation
Inagaki, S., Funato, M., Seki, J., Kawase, C., Ohuchi, K., Ando, S., Nakamura, S., Shimazawa, M., Kaneko, H., & Hara, H. (2019) · Neuroscience & Medicine · doi:10.4236/nm.2019.102010
Role of Optineurin In Metabotropic Glutamate Receptor 5-Regulated Autophagy
McLaren, C. (2020) · uO Research (University of Ottawa) · doi:10.20381/ruor-25103
Zhao, X. (2020) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.737211509.793579398
The Motor Neuron Diseases and Amyotrophic Lateral Sclerosis
Lewis, P. A., & Spillane, J. E. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-811069-0.00005-7 · Cited by 1
Molecular and clinical determinants of pathogenic protein aggregation
de Mattos, E. P. (2022) · University of Groningen research database (University of Groningen / Centre for Information Technology) · doi:10.33612/diss.220760500
Souza, A. C., Golbert, D. C. F., Cassoli, J. S., Sánchez-Gendriz, I., Lima, V. V. F., da Silva, F. A. C., Martins‐de‐Souza, D., & Ribeiro, S. T. G. (2022) · Research Square · doi:10.21203/rs.3.rs-1842393/v1
Co-chaperone BAG3 directly target autophagic degradation via its LC3-interacting regionsPreprint
Körschgen, H., Baeken, M. W., Schmitt, D., Nagel, H., & Behl, C. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.02.01.526551
Self-citationSeong, J., Kim, H., Lee, H. N., Ryu, H., & Inn, K. (2024) · Research Square · doi:10.21203/rs.3.rs-3998870/v1
PEX14 functions as a molecular link between optineurin and pexophagy in human cellsPreprint
Li, H., Chen, S., Lismont, C., Vandewinkel, B., Hussein, M. A. F., Costa, C. F., Imberechts, D., Liu, Y., Azevedo, J. E., Vandenberghe, W., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.05.31.596776
Gene Therapy for Neurodegeneration in Glaucoma
Karl, J. J., & Tseng, H. C. (2024) · Essentials in ophthalmology/Essentials ophthalmology · doi:10.1007/978-981-99-4436-1_21
Autophagy Receptors Couple Cargo Destined to Be Degraded with the Core Autophagy Machinery
Olsvik, H. L., Lamark, T., & Johansen, T. (2025) · Learning materials in biosciences · doi:10.1007/978-3-031-88121-3_4
In-vitro Reconstitution of Bacterial Ubiquitination and VCP/p97-mediated Elimination
Ghosh, S., Das, U. K., Rakshit, S., & Banerjee, A. (2026) · Journal of Visualized Experiments · doi:10.3791/69454
When optineurin meets innate immunity
Zhang, L., Han, J., Yang, Z., Xue, M., & Zheng, C. (2026) · Academia Immunity and Disease · doi:10.20935/acadimmunodis8165
Jeon, I. S., Lee, Y.-H., Hong, J. T., Kim, W. S., Shin, J.-C., Lee, H.-K., & Choi, J.-K. (2026) · Genes & Genomics · doi:10.1007/s13258-026-01755-x
Pourcelot, M. (2016) · theses.fr (ABES) · doi:10.70675/fe9bf786z6d4ez45d5zb047z4cff0d131b1c
Study of lymphocyte autophagy in normal and autoimmune responses
Murera, D. (2016) · theses.fr (ABES) · doi:10.70675/ab9d3ba4z5522z4d8aza5dbz681fe3fa1e44
Étude de l'autophagie lors d'une co-infection par le virus de la rougeole et Salmonella typhimurium
Clavière, M. (2018) · theses.fr (ABES) · doi:10.70675/478193d3zdbefz4e9dzaf20z16e9b2167fe3
Modulation de l'autophagie neuronale par la sérine protéase tPA en conditions ischémiques
Thiebaut, A. M. (2019) · theses.fr (ABES) · doi:10.70675/6586c0abz9e4cz455fz95ffzc52ec76397f8
Rôle du complexe VDAC1/TSPO1 au cours de l'érythropoïèse humaine, focus sur la mitophagie
Moras, M. (2020) · theses.fr (ABES) · doi:10.70675/a4c63cc2z949az4474zb1acz38e7f433fd35
Rôle de l’autophagie dans l’ostéosarcome
Camuzard, O. (2019) · theses.fr (ABES) · doi:10.70675/db9b0551zd9a2z4cf6z8dc4zdfbbe6b4e208
de Calbiac, H. (2019) · theses.fr (ABES) · doi:10.70675/bafe951fz8332z4b0azb55bzac8a4af1955b
Fonctions mitochondriales de la protéine Optineurine : neurodégénérescence et cancer
D’Urso, B. (2025) · theses.fr (ABES) · doi:10.70675/fe933860ze386z4ca5zaa6fzfcd35c62ce81
Abeydeera, N., Chin, J., Ruvalcaba, A., Amin, K., Nguyen, V. Q., Chang, J., Yin, K., Ernst, J. A., & Budzik, J. M. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.08.23.746595
BindingDB Entry 50008525: Discovery of BAY-985, a Highly Selective TBK1/IKKε Inhibitor.
BindingDB (2021) · UC San Diego · doi:10.7270/q2cn7795
Metadata
- Authors
- Korac, J., Schaeffer, V., Kovacevic, I., Clement, A. M., Jungblut, B., Behl, C., Terzic, J., & Dikic, I.
- Affiliations
- Department of Immunology and Medical Genetics, School of Medicine, University of Split, Soltanska 2, 21000 Split, Croatia
- Institute of Biochemistry II and Buchmann Institute for Molecular Life Sciences, School of Medicine, Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt (Main), Germany
- Johannes Gutenberg University Mainz (DE)
- Max Planck Institute for Heart and Lung Research (DE)
- Venue
- Journal of Cell Science
- Publisher
- The Company of Biologists
- Published
- 2013-01-15
- Volume
- 126
- Issue
- 2
- Pages
- 580-592
- ISSN
- 0021-9533 (ISSN-L)
- 1477-9137
- PMC
- PMC3654196
- OpenAlex
- W1985484942
- Cited by
- 336
- References
- 54
- Citations by year
- 2026: 6 · 2025: 21 · 2024: 25 · 2023: 15 · 2022: 25 · 2021: 25 · 2020: 35 · 2019: 31 · 2018: 25 · 2017: 26 · 2016: 35 · 2015: 37 · 2014: 20 · 2013: 10
- FWCI
- 15.99
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Journal of Cell Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Health Sciences › Medicine › Clinical Neurology › Amyotrophic Lateral Sclerosis Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Keywords
- optineurin, TBK1, protein aggregation, autophagy-lysosome pathway, coiled-coil domain, neurodegenerative diseases, amyotrophic lateral sclerosis, zebrafish model, TBK1 phosphorylation, protein inclusions
- MeSH terms
- Animals, Autophagy, Disease Models, Animal, HeLa Cells, Humans, Mice, Inbred C57BL, Mice, Transgenic, Phosphorylation, Protein Binding, Zebrafish, Cell Cycle Proteins, Neurodegenerative Diseases, Ubiquitin, Membrane Transport Proteins, Transcription Factor TFIIIA, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
