{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T22:58:16Z","timestamp":1791845896738,"version":"4.3.4"},"reference-count":43,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T00:00:00Z","timestamp":1771891200000},"content-version":"vor","delay-in-days":23,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Physiological Reports"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Glucocorticoids, such as dexamethasone (DEXA), are effective therapeutics but cause severe muscle wasting. Mitochondrial\u2010derived peptides (MDPs) are promising countermeasures, but their effectiveness is largely unexplored. We tested the hypothesis that the MDP S14G\u2010humanin (HNG) and the mitochondrial open reading frame of the 12S rRNA\u2010c (MOTS\u2010c) mitigate DEXA\u2010induced atrophy in human skeletal myotubes. Fully differentiated primary human myotubes were exposed to 10\u2009\u03bcM DEXA \u00b110\u2009\u03bcM HNG or 10\u2009\u03bcM MOTS\u2010c. DEXA decreased myotube size (area,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001) and differentiation (Fusion Index,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.05). Additionally, DEXA increased both muscle ring finger protein 1 (MURF1,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001) and muscle atrophy F\u2010box (MAFbx,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.01) as well as peroxisome proliferator\u2010activated receptor\u2010gamma coactivator\u20101 alpha (PGC1\u03b1,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). MOTS\u2010c co\u2010treatment with DEXA completely preserved myotube area (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001) and fusion index (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.02), increased Akt phosphorylation (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0015) and blunted both MURF1 upregulation (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.03) and STAT3 activation (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.005) compared to DEXA alone. HNG co\u2010treatment with DEXA preserved myotube area (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001), blunted DEXA\u2010induced STAT3 activation (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.027), but had no effect on fusion index or E3 ligase mRNA levels. Those findings suggest that MOTS\u2010c could be an effective inhibitor of glucocorticoid\u2010induced atrophy in human muscle, not only through selective inhibition of MURF1 but also by enhancing Akt signaling and suppressing STAT3 activation.\n                  <\/jats:p>","DOI":"10.14814\/phy2.70791","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T10:58:54Z","timestamp":1772967534000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Mitochondrial\u2010derived peptides\n                    <scp>MOTS<\/scp>\n                    \u2010c and humanin attenuate dexamethasone\u2010induced atrophy in human skeletal muscle cells"],"prefix":"10.14814","volume":"14","author":[{"given":"Rabie","family":"Elhusseiny","sequence":"first","affiliation":[{"name":"Institute of Neuroscience UCLouvain  Louvain\u2010la\u2010Neuve Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Ihsan","sequence":"additional","affiliation":[{"name":"Physical Education Department, College of Education United Arab Emirates Universit\u00e9  Al Ain UAE"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Th\u00e9o","family":"Bellefroid","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience UCLouvain  Louvain\u2010la\u2010Neuve Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulaziz","family":"Farooq","sequence":"additional","affiliation":[{"name":"Aspetar Orthopaedic and Sports Medicine Hospital Research and Scientific Support Department  Doha Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9bastien","family":"Racinais","sequence":"additional","affiliation":[{"name":"DMEM Univ Montpellier, INRAE  Montpellier France"},{"name":"Environmental Stress Unit CREPS Montpellier Font\u2010Romeu  Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3393-5278","authenticated-orcid":false,"given":"Louise","family":"Deldicque","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience UCLouvain  Louvain\u2010la\u2010Neuve Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,24]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.5455\/annalsmedres.2023.07.170"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2024.102534"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.13665"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00149.2020"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2013.05.018"},{"issue":"1","key":"e_1_2_13_7_1","first-page":"129","article-title":"Humanin prevents undesired apoptosis of chondrocytes without interfering with the anti\u2010inflammatory effect of dexamethasone in collagen\u2010induced arthritis","volume":"38","author":"Celvin B.","year":"2020","journal-title":"Clinical and experimental rheumatology"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424\u2010020\u201002367\u20104"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules25143267"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells8050406"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/metabo13010125"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2022.170840"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2021.130066"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox12030639"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00275.2020"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00285.2023"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2024.111212"},{"issue":"11","key":"e_1_2_13_18_1","article-title":"Stigmasterol protects against dexamethasone\u2010induced muscle atrophy by modulating the FoxO3\u2010MuRF1\/MAFbx signaling pathway in C2C12 Myotubes and mouse skeletal muscle","volume":"15","author":"Kwag S.\u2010J.","year":"2025","journal-title":"Biology and Life Sciences"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21072497"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jff.2023.105419"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1089\/jmf.2024.k.0168"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.21833"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.steroids.2019.01.004"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885\u2010016\u20102121\u20108"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.12688\/wellcomeopenres.15055.1"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/asj.12437"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460\u20109568.2003.02553.x"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12917\u2010019\u20101804\u20101"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btae658"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2010.11.061"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13105\u2010022\u201000925\u20101"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2014.181"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCO.0000000000000273"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms150611126"},{"key":"e_1_2_13_35_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tea.2015.0545"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.steroids.2011.03.002"},{"key":"e_1_2_13_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2021.108873"},{"key":"e_1_2_13_38_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0156225"},{"key":"e_1_2_13_39_1","doi-asserted-by":"publisher","DOI":"10.1042\/BSR20171056"},{"key":"e_1_2_13_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2010.10.006"},{"key":"e_1_2_13_41_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201801741R"},{"key":"e_1_2_13_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/mef2.70008"},{"key":"e_1_2_13_43_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1120533"},{"key":"e_1_2_13_44_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.823354"}],"container-title":["Physiological Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.14814\/phy2.70791","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/full-xml\/10.14814\/phy2.70791","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.14814\/phy2.70791","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T10:37:59Z","timestamp":1777718279000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.14814\/phy2.70791"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2]]},"references-count":43,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["10.14814\/phy2.70791"],"URL":"https:\/\/doi.org\/10.14814\/phy2.70791","archive":["Portico"],"relation":{},"ISSN":["2051-817X","2051-817X"],"issn-type":[{"value":"2051-817X","type":"print"},{"value":"2051-817X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2]]},"assertion":[{"value":"2025-10-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-09","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-24","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70791"}}