Impaired disassembly of the axon initial segment restricts mitochondrial entry into damaged axons.

ABSTRACT: The proteasome is essential for cellular responses to various physiological stressors. However, how proteasome function impacts the stress resilience of regenerative damaged motor neurons remains unclear. Here, we develop a unique mouse model using a regulatory element of the activating transcription factor (Atf3) gene to label mitochondria in a damage-induced manner while simultaneously genetically disrupting the proteasome. Using this model, we observed that in injury-induced proteasome-deficient mouse motor neurons, the increase of mitochondrial influx from soma into axons is inhibited because neurons fail to disassemble ankyrin G, an organizer of the axon initial segment (AIS), in a proteasome-dependent manner. Further, these motor neurons exhibit amyotrophic lateral sclerosis (ALS)-li

SUBMITTER: Kiryu-Seo S 

PROVIDER: S-EPMC9574747 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature