{"created":"2023-06-19T10:43:59.039313+00:00","id":4343,"links":{},"metadata":{"_buckets":{"deposit":"de641080-bec7-4159-810e-00f45c06a1a2"},"_deposit":{"created_by":11,"id":"4343","owners":[11],"pid":{"revision_id":0,"type":"depid","value":"4343"},"status":"published"},"_oai":{"id":"oai:shiga-med.repo.nii.ac.jp:00004343","sets":["19:82:83","30:198:199","30:436:437"]},"author_link":["7237","9059","7326","7226","7324","9166","7327","8970","9168","6171","6506","8967","9167","1956"],"item_4_biblio_info_6":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2022-09-26","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"1","bibliographicVolumeNumber":"12","bibliographic_titles":[{},{"bibliographic_title":"Scientific reports","bibliographic_titleLang":"en"}]}]},"item_4_creator_3":{"attribute_name":"著者別名","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"引網, 亮太"}],"nameIdentifiers":[{},{}]},{"creatorNames":[{"creatorName":"守村, 敏史"}],"nameIdentifiers":[{},{}]},{"creatorNames":[{"creatorName":"築山, 智之"}],"nameIdentifiers":[{},{},{}]},{"creatorNames":[{"creatorName":"守村, 直子"}],"nameIdentifiers":[{},{}]},{"creatorNames":[{"creatorName":"楠井, 真季子"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"和田, 英貴"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"小代, 明美"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"浅田, めぐみ"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"漆谷, 真"}],"nameIdentifiers":[{},{},{}]}]},"item_4_description_14":{"attribute_name":"フォーマット","attribute_value_mlt":[{"subitem_description":"pdf","subitem_description_type":"Other"}]},"item_4_description_4":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"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. ","subitem_description_type":"Abstract"}]},"item_4_description_42":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"subitem_description":"Journal Article","subitem_description_type":"Other"}]},"item_4_publisher_32":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"Springer Nature"}]},"item_4_relation_10":{"attribute_name":"PubMed番号","attribute_value_mlt":[{"subitem_relation_type":"isIdenticalTo","subitem_relation_type_id":{"subitem_relation_type_id_text":"36163369","subitem_relation_type_select":"PMID"}}]},"item_4_relation_11":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_name":[{"subitem_relation_name_text":"10.1038/s41598-022-20405-2"}],"subitem_relation_type":"isIdenticalTo","subitem_relation_type_id":{"subitem_relation_type_id_text":"https://doi.org/10.1038/s41598-022-20405-2","subitem_relation_type_select":"DOI"}}]},"item_4_relation_13":{"attribute_name":"PMCID","attribute_value_mlt":[{"subitem_relation_name":[{"subitem_relation_name_text":"PMC9512926"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"http://www.ncbi.nlm.nih.gov/pmc/articles/pmc9512926/","subitem_relation_type_select":"URI"}}]},"item_4_rights_12":{"attribute_name":"権利","attribute_value_mlt":[{"subitem_rights":"© 2022. The Author(s). "}]},"item_4_source_id_7":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"2045-2322","subitem_source_identifier_type":"ISSN"}]},"item_4_version_type_15":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"HIKIAMI, Ryota"}],"nameIdentifiers":[{},{}]},{"creatorNames":[{"creatorName":"MORIMURA, Toshifumi"}],"nameIdentifiers":[{},{}]},{"creatorNames":[{"creatorName":"AYAKI, Takashi"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"TSUKIYAMA, Tomoyuki"}],"nameIdentifiers":[{},{},{}]},{"creatorNames":[{"creatorName":"MORIMURA, Naoko"}],"nameIdentifiers":[{},{}]},{"creatorNames":[{"creatorName":"KUSUI, Makiko"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"WADA, Hideki"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"MINAMIYAMA, Sumio"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"SHODAI, Akemi"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"ASADA-UTSUGI, Megumi"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"MURAMATSU, Shin-Ichi"}],"nameIdentifiers":[{},{},{}]},{"creatorNames":[{"creatorName":"UEKI, Takatoshi"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Takahashi, Ryosuke"}],"nameIdentifiers":[{},{},{}]},{"creatorNames":[{"creatorName":"URUSHITANI, Makoto"}],"nameIdentifiers":[{},{},{}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2022-10-13"}],"displaytype":"detail","filename":"s41598-022-20405-2.pdf","filesize":[{"value":"3.2 MB"}],"format":"application/pdf","license_note":"This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit \nhttp://creativecommons.org/licenses/by/4.0/.","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"s41598-022-20405-2","url":"https://shiga-med.repo.nii.ac.jp/record/4343/files/s41598-022-20405-2.pdf"},"version_id":"09cf7adf-4935-41a4-bece-bf16dd11c38a"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"Chemical biology","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Mechanisms of disease","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Neurological disorders","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Neuroscience","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Protein folding","subitem_subject_language":"en","subitem_subject_scheme":"Other"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"journal article","resourceuri":"http://purl.org/coar/resource_type/c_6501"}]},"item_title":"Conformational change of RNA-helicase DHX30 by ALS/FTD-linked FUS induces mitochondrial dysfunction and cytosolic aggregates.","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Conformational change of RNA-helicase DHX30 by ALS/FTD-linked FUS induces mitochondrial dysfunction and cytosolic aggregates."}]},"item_type_id":"4","owner":"11","path":["83","199","437"],"pubdate":{"attribute_name":"公開日","attribute_value":"2022-10-13"},"publish_date":"2022-10-13","publish_status":"0","recid":"4343","relation_version_is_last":true,"title":["Conformational change of RNA-helicase DHX30 by ALS/FTD-linked FUS induces mitochondrial dysfunction and cytosolic aggregates."],"weko_creator_id":"11","weko_shared_id":-1},"updated":"2023-06-19T11:10:57.318025+00:00"}