{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T12:20:09Z","timestamp":1787746809232,"version":"build-2784847793"},"reference-count":27,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T00:00:00Z","timestamp":1783641600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T00:00:00Z","timestamp":1783641600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF\u2010RS\u20102024\u201000349251"],"award-info":[{"award-number":["NRF\u2010RS\u20102024\u201000349251"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004230","name":"Korea Polar Research Institute","doi-asserted-by":"publisher","award":["PE26160"],"award-info":[{"award-number":["PE26160"]}],"id":[{"id":"10.13039\/501100004230","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002631","name":"Gachon University","doi-asserted-by":"publisher","award":["GCU\u2010202300580001"],"award-info":[{"award-number":["GCU\u2010202300580001"]}],"id":[{"id":"10.13039\/501100002631","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Dnajb5, a member of the heat shock protein family, has not been previously reported to play a role in muscle differentiation. We identify Dnajb5 as a negative regulator of myogenesis via mammalian target of rapamycin (mTOR) and histone deacetylase 4 (HDAC4) signalling, functioning as a central controller of muscle growth and metabolism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      mTOR\u2010binding proteins were screened by mass spectrometry in Antarctic fish (\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>Notothenia coriiceps<\/jats:italic>\n                      <\/jats:styled-content>\n                      ) muscle extracts. Functional roles of Dnajb5 were examined in C2C12 and primary myoblasts using shRNA\u2010mediated knockdown. In\u00a0vivo effects were analysed using a BaCl\n                      <jats:sub>2<\/jats:sub>\n                      \u2010induced muscle injury model in mice (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20096\u201312 per group).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Mass spectrometry identified Dnajb5 as an mTOR\u2010binding protein. This interaction was conserved in mammalian cells and weakened by hydrogen peroxide (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). Dnajb5 knockdown in C2C12 myoblasts selectively increased S6K1 phosphorylation without altering basal Akt phosphorylation. Myogenic differentiation increased, characterized by upregulated\n                      <jats:italic>Myog<\/jats:italic>\n                      ,\n                      <jats:italic>Igf2<\/jats:italic>\n                      and\n                      <jats:italic>Ckm<\/jats:italic>\n                      expression (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05) and elevated differentiation index (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). In\u00a0vivo, Dnajb5 depletion improved tibialis anterior muscle regeneration, increasing regenerating fibre cross\u2010sectional area by approximately 26% at Day 5 post\u2010injury (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). Dnajb5 knockdown increased\n                      <jats:italic>Ppargc1a<\/jats:italic>\n                      expression via release of mTORC1 inhibition and preventing the nuclear retention of HDAC4. Mitochondrial DNA copy number increased 1.3\u2010fold (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05), and oxidative enzyme activity rose significantly (succinate dehydrogenase\u2010positive fibres: 2.8\u2010fold (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01), cytochrome c oxidase\u2010positive fibres: 1.4\u2010fold (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). Grip strength improved by 14% (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05), and rotarod endurance increased by 31% (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01) relative to controls.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Dnajb5 functions as a negative regulator of muscle differentiation and regeneration by coordinating mTORC1 signalling and the HDAC4\u2010MEF2 axis. These findings reveal a redox\u2010sensitive dual\u2010pathway mechanism linking protein synthesis and mitochondrial biogenesis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.70332","type":"journal-article","created":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T05:01:06Z","timestamp":1783746066000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dnajb5 From Antarctic Fish Reveals a Redox\u2010Sensitive Mechanism Coordinating Muscle Regeneration via mTORC1 and HDAC4"],"prefix":"10.1002","volume":"17","author":[{"given":"Sun\u2010Hee","family":"Cho","sequence":"first","affiliation":[{"name":"Department of Health Sciences and Technology, Gachon Advanced Institute for Health Science &amp; Technology Gachon University  Incheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min\u2010Kyung","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine Gachon University College of Medicine  Incheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi\u2010Ock","family":"Baek","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine Gachon University College of Medicine  Incheon Republic of Korea"},{"name":"Lee Gil Ya Cancer and Diabetes Institute Gachon University  Incheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyeon\u2010Hee","family":"Son","sequence":"additional","affiliation":[{"name":"Department of Bio\u2010Medical Science Gachon University College of Medicine  Incheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binh Thanh","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Center for Advanced Biomolecular Recognition Korea Institute of Science and Technology (KIST)  Seoul Republic of Korea"},{"name":"Division of Bio\u2010Medical Science and Technology Korea University of Science and Technology (UST)  Daejeon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min\u2010Jung","family":"Kang","sequence":"additional","affiliation":[{"name":"Center for Advanced Biomolecular Recognition Korea Institute of Science and Technology (KIST)  Seoul Republic of Korea"},{"name":"Division of Bio\u2010Medical Science and Technology Korea University of Science and Technology (UST)  Daejeon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Il\u2010Chan","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Life Sciences Korea Polar Research Institute  Incheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin\u2010Hyoung","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Life Sciences Korea Polar Research Institute  Incheon Republic of Korea"},{"name":"Polar Science University of Science and Technology  Incheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0114-1142","authenticated-orcid":false,"given":"Mee\u2010Sup","family":"Yoon","sequence":"additional","affiliation":[{"name":"Department of Health Sciences and Technology, Gachon Advanced Institute for Health Science &amp; Technology Gachon University  Incheon Republic of Korea"},{"name":"Department of Molecular Medicine Gachon University College of Medicine  Incheon Republic of Korea"},{"name":"Lee Gil Ya Cancer and Diabetes Institute Gachon University  Incheon Republic of Korea"},{"name":"Department of Bio\u2010Medical Science Gachon University College of Medicine  Incheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,10]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.02.004"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2017.00788"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C100406200"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200912093"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.4161\/15384101.2014.991572"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M603536200"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature06322"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2013.03.003"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1546-5098(04)22004-0"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/icb\/icq038"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2006.1946"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1242\/jeb.116129"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jff.2023.105483"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12947"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24065506"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241612602"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0337639100"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.07.023"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgg.2020.07.005"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.04.041"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbapap.2025.141074"},{"key":"e_1_2_7_23_1","first-page":"4470","article-title":"Inhibition of DNAJ\u2010HSP70 Interaction Improves Strength in Muscular Dystrophy","volume":"130","author":"Bengoechea R.","year":"2020","journal-title":"Journal of Clinical Investigation"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.32991"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12223"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00031.2007"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2020.101477"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01608-z"}],"container-title":["Journal of Cachexia, Sarcopenia and Muscle"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcsm.70332","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcsm.70332","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcsm.70332","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T11:32:01Z","timestamp":1787743921000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcsm.70332"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,10]]},"references-count":27,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1002\/jcsm.70332"],"URL":"https:\/\/doi.org\/10.1002\/jcsm.70332","archive":["Portico"],"relation":{},"ISSN":["2190-5991","2190-6009"],"issn-type":[{"value":"2190-5991","type":"print"},{"value":"2190-6009","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,10]]},"assertion":[{"value":"2025-09-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70332"}}