DnaJC7 Antagonizes the Toxic Effects of Proteostasis Stress

DnaJC7 is a co-chaperone implicated in a neurodegenerative disease called Amyotrophic Lateral Sclerosis (ALS). The aim of my research was to discover its role in protein homeostasis, and how DnaJC7 contributes to preventing protein homeostasis failure. To this end, we employed both a yeast and SH-SY5Y mammalian cell model to track the localization of DnaJC7, expression and its protection against toxicity. In both models, we found that DnaJC7 changes localization under conditions that increase protein misfolding within the cell. Also, under conditions of stress that illicit an increase in proteostatic stress, DnaJC7 can reduce the ensuing cellular toxicity. Several ALS-associated variants of DnaJC7 were unable to recover the toxicity, and many were significantly degraded under basal conditions compared to wild-type DnaJC7. We conclude that DnaJC7 has a protective role during protein homeostasis failure, providing a new potential therapeutic target for treating ALS disease.