ArticlePloS one2015
A Glaucoma-Associated Variant of Optineurin, M98K, Activates Tbk1 to Enhance Autophagosome Formation and Retinal Cell Death Dependent on Ser177 Phosphorylation of Optineurin.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 50 citations in OpenAlex.
- Optineurin calibrates STING-mediated type I interferon response.The FEBS journal · 2026Article
- OPTN protects retinal ganglion cells and ameliorates neuroinflammation in optic neuropathies.Communications biology · 2025Article
- Article
- New Insights into the Role of Cellular Senescence and Its Therapeutic Implications in Ocular Diseases.Bioengineering (Basel, Switzerland) · 2025Review
- Tank-binding kinase 1 regulates inflammation and autophagy in glaucoma.Frontiers in neuroscience · 2025Review
- Protein misfolding and mitochondrial dysfunction in glaucoma.Frontiers in cell and developmental biology · 2025Review
- Extracellular release in the quality control of the mammalian mitochondria.Journal of biomedical science · 2023Review
- TBK1 Knockdown Alleviates Axonal Transport Deficits in Retinal Ganglion Cells Via mTORC1 Activation in a Retinal Damage Mouse Model.Investigative ophthalmology & visual science · 2023Article
- Proteostasis in aging-associated ocular disease.Molecular aspects of medicine · 2022Review
- The Role of Autophagy in Eye Diseases.Life (Basel, Switzerland) · 2021Review
- Neuroinflammatory Mechanisms of Mitochondrial Dysfunction and Neurodegeneration in Glaucoma.Journal of ophthalmology · 2021Review
- Article
- Acteoside inhibits autophagic apoptosis of retinal ganglion cells to rescue glaucoma-induced optic atrophy.Journal of cellular biochemistry · 2019Article
- Autophagy as a common pathway in amyotrophic lateral sclerosis.Neuroscience letters · 2019Review
- Maternal Flavonoids Intake Reverts Depression-Like Behaviour in Rat Female Offspring.Nutrients · 2019Article
- Coding Region Mutation Screening in Optineurin in Chinese Normal-Tension Glaucoma Patients.Disease markers · 2019Article
- Autophagy and Age-Related Eye Diseases.BioMed research international · 2019Review
- Optineurin promotes autophagosome formation by recruiting the autophagy-related Atg12-5-16L1 complex to phagophores containing the Wipi2 protein.The Journal of biological chemistry · 2018Article
- Contribution of autophagy to ocular hypertension and neurodegeneration in the DBA/2J spontaneous glaucoma mouse model.Cell death discovery · 2018Article
- Autophagy receptor optineurin promotes autophagosome formation by potentiating LC3-II production and phagophore maturation.Communicative & integrative biology · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Certain missense mutations in optineurin/OPTN and amplification of TBK1 are associated with normal tension glaucoma. A glaucoma-associated variant of OPTN, M98K, induces autophagic degradation of transferrin receptor (TFRC) and death in retinal cells. Here, we have explored the role of Tbk1 in M98K-OPTN-induced autophagy and cell death, and the effect of Tbk1 overexpression in retinal cells. Cell death induced by M98K-OPTN was dependent on Tbk1 as seen by the effect of Tbk1 knockdown and blocking of Tbk1 activity by a chemical inhibitor. Inhibition of Tbk1 also restores M98K-OPTN-induced transferrin receptor degradation. M98K-OPTN-induced autophagosome formation, autophagy and cell death were dependent on its phosphorylation at S177 by Tbk1. Knockdown of OPTN reduced starvation-induced autophagosome formation. M98K-OPTN expressing cells showed higher levels of Tbk1 activation and enhanced phosphorylation at Ser177 compared to WT-OPTN expressing cells. M98K-OPTN-induced activation of Tbk1 and its ability to be phosphorylated better by Tbk1 was dependent on ubiquitin binding. Phosphorylated M98K-OPTN localized specifically to autophagosomes and endogenous Tbk1 showed increased localization to autophagosomes in M98K-OPTN expressing cells. Overexpression of Tbk1 induced cell death and caspase-3 activation that were dependent on its catalytic activity. Tbk1-induced cell death possibly involves autophagy, as shown by the effect of Atg5 knockdown, and requirement of autophagic function of OPTN. Our results show that phosphorylation of Ser177 plays a crucial role in M98K-OPTN-induced autophagosome formation, autophagy flux and retinal cell death. In addition, we provide evidence for cross talk between two glaucoma associated proteins and their inter-dependence to mediate autophagy-dependent cell death.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.