Aberrant phase separation leads to lysosome sequestering and acidification

Abstract

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that leads to the death of upper and lower motor neurons. While most cases of ALS are sporadic, some of the familial forms of the disease are caused by mutations in the gene encoding for the RNA-binding protein FUS. Under physiological conditions, FUS readily phase separates into liquid-like droplets. ALS-associated mutations interfere with this process and often result in solid-like aggregates rather than fluid condensates.