@article{oai:shiga-med.repo.nii.ac.jp:00004343,
 author = {引網, 亮太 and 守村, 敏史 and 築山, 智之 and 守村, 直子 and 楠井, 真季子 and 和田, 英貴 and 小代, 明美 and 浅田, めぐみ and 漆谷, 真 and HIKIAMI, Ryota and MORIMURA, Toshifumi and AYAKI, Takashi and TSUKIYAMA, Tomoyuki and MORIMURA, Naoko and KUSUI, Makiko and WADA, Hideki and MINAMIYAMA, Sumio and SHODAI, Akemi and ASADA-UTSUGI, Megumi and MURAMATSU, Shin-Ichi and UEKI, Takatoshi and Takahashi, Ryosuke and URUSHITANI, Makoto},
 issue = {1},
 journal = {Scientific reports},
 month = {Sep},
 note = {pdf, Genetic mutations in fused in sarcoma (FUS) cause amyotrophic lateral sclerosis (ALS). Although mitochondrial dysfunction and stress granule have been crucially implicated in FUS proteinopathy, the molecular basis remains unclear. Here, we show that DHX30, a component of mitochondrial RNA granules required for mitochondrial ribosome assembly, interacts with FUS, and plays a crucial role in ALS-FUS. WT FUS did not affect mitochondrial localization of DHX30, but the mutant FUS lowered the signal of mitochondrial DHX30 and promoted the colocalization of cytosolic FUS aggregates and stress granule markers. The immunohistochemistry of the spinal cord from an ALS-FUS patient also confirmed the colocalization, and the immunoelectron microscope demonstrated decreased mitochondrial DHX30 signal in the spinal motor neurons. Subcellular fractionation by the detergent-solubility and density-gradient ultracentrifugation revealed that mutant FUS also promoted cytosolic mislocalization of DHX30 and aggregate formation. Interestingly, the mutant FUS disrupted the DHX30 conformation with aberrant disulfide formation, leading to impaired mitochondrial translation. Moreover, blue-native gel electrophoresis revealed an OXPHOS assembly defect caused by the FUS mutant, which was similar to that caused by DHX30 knockdown. Collectively, our study proposes DHX30 as a pivotal molecule in which disulfide-mediated conformational change mediates mitochondrial dysfunction and cytosolic aggregate formation in ALS-FUS., Journal Article},
 title = {Conformational change of RNA-helicase DHX30 by ALS/FTD-linked FUS induces mitochondrial dysfunction and cytosolic aggregates.},
 volume = {12},
 year = {2022}
}