FUS Interacts with HSP60 to Promote Mitochondrial Damage
作者： Qi Xu , Sidan Du , Kazuo Fushimi , Li Zhu , Jane Y. Wu
DOI: 10.1371/JOURNAL.PGEN.1005357
关键词:
摘要: FUS-proteinopathies, a group of heterogeneous disorders including ALS-FUS and FTLD-FUS, are characterized by the formation inclusion bodies containing nuclear protein FUS in affected patients. However, underlying molecular cellular defects remain unclear. Here we provide evidence for mitochondrial localization its induction damage. Remarkably, FTLD-FUS brain samples show increased expression defects. Biochemical genetic data demonstrate that interacts with chaperonin, HSP60, translocation to mitochondria is, at least part, mediated HSP60. Down-regulating HSP60 reduces mitochondrially localized partially rescues neurodegenerative phenotypes caused transgenic flies. This is first report direct targeting associated neurodegeneration, suggesting impairment may represent critical event different forms FUS-proteinopathies common pathological feature both FTLD-FUS. Our study offers potential explanation highly nature complex presentation FUS-proteinopathies. also suggest damage be target future development diagnostic therapeutic tools devastating diseases.
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