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FUS interacts with ATP synthase beta subunit and induces mitochondrial unfolded protein response in cellular and animal models, PNAS, 24 Sep 2018
2018-09-25 | 【     】【打印】【关闭

PNAS, 24 Sep 2018,DOI: https://doi.org/10.1073/pnas.1806655115

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

Jianwen Deng#, Peng Wang#, Xiaoping Chen, Haipeng Cheng, Jianghong Liu, Kazuo Fushimi, Li Zhu*, and Jane Y. Wu*

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 (UPRmt). Importantly, down-regulating expression of ATP5B or UPRmt 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.

文章链接:http://www.pnas.org/content/early/2018/09/20/1806655115

相关报道:http://www.ibp.cas.cn/kyjz/zxdt/201809/t20180925_5097575.html

 

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