Axonal mitochondria delivery by Optineurin promotes neuroprotection and axon regeneration

Amyotrophic lateral sclerosis (ALS) and normal tension glaucoma (NTG) are linked to various Optineurin (OPTN) mutations, but the molecular mechanisms underlying neurodegeneration is not well understood. 

The researchers find that OPTN C-terminus truncation (OPTNΔC) 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.

They discover that OPTN C-terminus directly interacts with both microtubules and the mitochondrial transport complex TRAK1/KIF5B, stabilizing them for proper anterograde axonal mitochondrial transport.

Furthermore, overexpressing OPTN/TRAK1/KIF5B prevents not only OPTN truncation-induced, but also ocular hypertension-induced neurodegeneration, and promotes robust ON regeneration.

https://www.nature.com/articles/s41467-025-57135-8

https://sciencemission.com/Optineurin-facilitated-axonal-mitochondria-delivery