Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.6.3.14 (
ATP synthase
)
7,042
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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 UPR
mt
genes in
FUS
transgenic flies ameliorates neurodegenerative phenotypes. Our data show that mitochondrial impairment is a critical early event in
FUS
proteinopathy, and provide insights into the pathogenic mechanism of
FUS
-induced neurodegeneration.
...
PMID:FUS interacts with ATP synthase beta subunit and induces mitochondrial unfolded protein response in cellular and animal models. 3024 57
