Dong Liu, Hannah C Webber, Fuyun Bian, Yangfan Xu, Manjari Prakash, Xue Feng, Ming Yang, Hang Yang, In-Jee You, Liang Li, Liping Liu, Pingting Liu, Haoliang Huang, Chien-Yi Chang, Liang Liu, Sahil H Shah, Anna La Torre, Derek S Welsbie, Yang Sun, Xin Duan, Jeffrey Louis Goldberg, Marcus Braun, Zdenek Lansky, Yang Hu
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 (OPTNΔC) 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...
April 3, 2024: bioRxiv