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  • Academic
    University - Academic staff Department: Ophthalmology Research/Clinical Trials Position: Basic Life Research Scientist

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  • Mail Code: 5353

All Publications

  • Optineurin-facilitated axonal mitochondria delivery promotes neuroprotection and axon regeneration. Nature communications 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. 2025; 16 (1): 1789

    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 find 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 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.

    View details for DOI 10.1038/s41467-025-57135-8

    View details for PubMedID 39979261

    View details for PubMedCentralID 3714538

  • Optineurin-facilitated axonal mitochondria delivery promotes neuroprotection and axon regeneration. bioRxiv : the preprint server for biology Liu, D., Webber, H. C., Bian, F., Xu, Y., Prakash, M., Feng, X., Yang, M., Yang, H., You, I., Li, L., Liu, L., Liu, P., Huang, H., Chang, C., Liu, L., Shah, S. H., Torre, A. L., Welsbie, D. S., Sun, Y., Duan, X., Goldberg, J. L., Braun, M., Lansky, Z., Hu, Y. 2024

    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.

    View details for DOI 10.1101/2024.04.02.587832

    View details for PubMedID 38617277