Optineurin-facilitated axonal mitochondria delivery promotes neuroprotection and axon regeneration
Open accessPublished version of a preprint
Abstract
Optineurin (OPTN) mutations are linked to amyotrophic lateral sclerosis (ALS) and normal tension glaucoma (NTG), but a relevant animal model is lacking, and the molecular mechanisms underlying neurodegeneration are unknown. We found that OPTN C-terminus truncation (OPTN∆C) causes late-onset neurodegeneration of retinal ganglion cells (RGCs), optic nerve (ON), and spinal cord motor neurons, preceded by a striking decrease of axonal mitochondria. Surprisingly, we discover that OPTN directly interacts with both microtubules and the mitochondrial transport complex TRAK1/KIF5B, stabilizing them for proper anterograde axonal mitochondrial transport, in a C-terminus dependent manner. Encouragingly, overexpressing OPTN/TRAK1/KIF5B reverses not only OPTN truncation-induced, but also ocular hypertension-induced neurodegeneration, and promotes striking ON regeneration. Therefore, in addition to generating new animal models for NTG and ALS, our results establish OPTN as a novel facilitator of the microtubule-dependent mitochondrial transport necessary for adequate axonal mitochondria delivery, and its loss as the likely molecular mechanism of neurodegeneration.
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
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.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 114 · Cited by 34
- Authors
- Liu, D., Webber, H. C., Bian, F., Xu, Y., Prakash, M., Feng, X., Yang, M., Yang, H., You, I.-J., Li, L., Liu, L., Liu, P., Huang, H., Chang, C.-Y., Liu, L., Shah, S. H., La Torre, A., Welsbie, D. S., Sun, Y., Duan, X., Goldberg, J. L., Braun, M., Lansky, Z., & Hu, Y.
- Affiliations
- Stanford University (US)
- Shanghai Medical College of Fudan University (CN)
- Czech Academy of Sciences (CZ)
- University of California San Diego (US)
- University of California, San Francisco (US)
- Stanford Medicine (US)
- Corresponding author
- Hu, Yang
- ORCID
- Venue
- Nature Communications
- Published
- 2025-02-20
- Volume
- 16
- Issue
- 1
- Pages
- 1789-1789
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC11842812
- OpenAlex
- W4407796432
- Cited by
- 34
- References
- 114
- Citations by year
- 2026: 18 · 2025: 14 · 2024: 2
- FWCI
- 27.00
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nature Communications (publishedVersion, cc-by-nc-nd)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion, cc-by-nc-nd)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Durham Research Online (Durham University) (submittedVersion)
- Funders
- U.S. Department of Health & Human Services | NIH | National Eye Institute (EY024932, EY034353, 1F32EY029567, EY026877, EY032518, EY023295)
- Topics
- Health Sciences › Medicine › Ophthalmology › Glaucoma and retinal disorders
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
- Keywords
- optineurin, microtubule stabilization, neurodegeneration, retinal ganglion cells, optic nerve regeneration, amyotrophic lateral sclerosis, normal-tension glaucoma, ocular hypertension, axon protection, animal models
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
