FUS interacts with ATP synthase beta subunit and induces mitochondrial unfolded protein response in cellular and animal models.

ABSTRACT: FUS (fused in sarcoma) proteinopathy is a group of neurodegenerative diseases characterized by the formation of inclusion bodies containing the FUS protein, including frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Previous studies show that mitochondrial damage is an important aspect of FUS proteinopathy. However, the molecular mechanisms by which FUS induces mitochondrial damage remain to be elucidated. Our biochemical and genetic experiments demonstrate that FUS interacts with the catalytic subunit of mitochondrial ATP synthase (ATP5B), disrupts the formation of ATP synthase complexes, and inhibits mitochondrial ATP synthesis. FUS expression activates the mitochondrial unfolded protein response (UPR^mt). Importantly, down-regulating expression of ATP5B or

SUBMITTER: Deng J 

PROVIDER: S-EPMC6187197 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature