Optineurin-facilitated axonal mitochondria delivery promotes neuroprotection and axon regeneration
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F86652036%3A_____%2F25%3A00638983" target="_blank" >RIV/86652036:_____/25:00638983 - isvavai.cz</a>
Result on the web
<a href="https://www.nature.com/articles/s41467-025-57135-8" target="_blank" >https://www.nature.com/articles/s41467-025-57135-8</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s41467-025-57135-8" target="_blank" >10.1038/s41467-025-57135-8</a>
Alternative languages
Result language
angličtina
Original language name
Optineurin-facilitated axonal mitochondria delivery promotes neuroprotection and axon regeneration
Original language description
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 find that OPTN C-terminus truncation (OPTNC) causes late-onset neurodegeneration of retinal ganglion cells (RGCs), optic nerve (ON), and spinal cord motor neurons, preceded by a decrease of axonal mitochondria in mice. 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. Furthermore, overexpressing OPTN/TRAK1/KIF5B prevents not only OPTN truncation-induced, but also ocular hypertension-induced neurodegeneration, and promotes robust ON regeneration. Therefore, in addition to generating animal models for NTG and ALS, our results establish OPTN as a facilitator of the microtubule-dependent mitochondrial transport necessary for adequate axonal mitochondria delivery, and its loss as the likely molecular mechanism of neurodegeneration.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10601 - Cell biology
Result continuities
Project
<a href="/en/project/EF18_046%2F0015974" target="_blank" >EF18_046/0015974: Upgrading Czech Infrastructure for Integrative Structural Biology</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Nature Communications
ISSN
2041-1723
e-ISSN
2041-1723
Volume of the periodical
16
Issue of the periodical within the volume
1
Country of publishing house
DE - GERMANY
Number of pages
23
Pages from-to
1789
UT code for WoS article
001509296900026
EID of the result in the Scopus database
2-s2.0-85218501739