{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T03:09:04Z","timestamp":1790824144275,"version":"4.1.0"},"reference-count":39,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T00:00:00Z","timestamp":1761609600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T00:00:00Z","timestamp":1761609600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2025,12]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n Skeletal muscle aging is associated with oxidative stress and mitochondrial dysfunction. Peroxiredoxins (PRDXs), particularly PRDX3 and PRDX5, are antioxidant enzymes that are uniquely localized to mitochondria. While PRDX3 has been reported to play a role in maintaining mitochondrial function in muscle, the specific function of PRDX5 in muscle remains unclear. This study investigated the role of PRDX5 in mitochondrial function, myonuclear distribution and muscle aging.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Myoblasts were isolated from wild\u2010type (WT),\n Prdx3<\/jats:italic>\n \n \u2212\/\u2212<\/jats:italic>\n <\/jats:sup>\n ,\n Prdx5<\/jats:italic>\n \n \u2212\/\u2212<\/jats:italic>\n <\/jats:sup>\n and\n Prdx3<\/jats:italic>\n \n \u2212\/\u2212<\/jats:italic>\n <\/jats:sup>\n ;\n Prdx5<\/jats:italic>\n \n \u2212\/\u2212<\/jats:italic>\n <\/jats:sup>\n mice crossed with mitochondria reporter (mt\u2010GFP) mice. Nuclear and mitochondrial positioning were evaluated using confocal and super\u2010resolution lattice structured illumination microscopy (SIM). Mitochondrial function was assessed by Seahorse oxygen consumption rates (OCR) assays. In\u00a0vivo analyses included grip strength, treadmill performance and histological evaluation following venom\u2010induced muscle injury.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n During myogenesis,\n Prdx5<\/jats:italic>\n \n \u2212\/\u2212<\/jats:italic>\n <\/jats:sup>\n and\n Prdx3<\/jats:italic>\n \n \u2212\/\u2212<\/jats:italic>\n <\/jats:sup>\n ;\n Prdx5<\/jats:italic>\n \n \u2212\/\u2212<\/jats:italic>\n <\/jats:sup>\n myotubes exhibited impairments in nuclear spreading, characterized by clustered nuclei, unlike the even distribution observed in WT and\n Prdx3<\/jats:italic>\n \n \u2212\/\u2212<\/jats:italic>\n <\/jats:sup>\n myotubes (44.4% and 44.9% vs. 17.1% and 21.9%, respectively;\n p<\/jats:italic>\n \u2009<\u20090.001). Mitochondrial ATP production was significantly reduced in\n Prdx3<\/jats:italic>\n \n \u2212\/\u2212<\/jats:italic>\n <\/jats:sup>\n ,\n Prdx5<\/jats:italic>\n \n \u2212\/\u2212<\/jats:italic>\n <\/jats:sup>\n and\n Prdx3<\/jats:italic>\n \n \u2212\/\u2212<\/jats:italic>\n <\/jats:sup>\n ;\n Prdx5<\/jats:italic>\n \n \u2212\/\u2212<\/jats:italic>\n <\/jats:sup>\n myotubes (\n p<\/jats:italic>\n \u2009<\u20090.05). The expression of\n Rhot1<\/jats:italic>\n and\n Trak1<\/jats:italic>\n , key regulators of mitochondrial transport, was significantly decreased in\n Prdx5<\/jats:italic>\n \n \u2212\/\u2212<\/jats:italic>\n <\/jats:sup>\n and\n Prdx3<\/jats:italic>\n \n \u2212\/\u2212<\/jats:italic>\n <\/jats:sup>\n ;\n Prdx5<\/jats:italic>\n \n \u2212\/\u2212<\/jats:italic>\n <\/jats:sup>\n myotubes (\n p<\/jats:italic>\n \u2009<\u20090.01). Knockdown of\n Rhot1<\/jats:italic>\n or\n Trak1<\/jats:italic>\n in WT myotubes led to myonuclear clustering similar to that observed in\n Prdx5<\/jats:italic>\n \u2010deficient myotubes, supporting that PRDX5 facilitates mitochondrial transport and nuclear positioning, at least in part, through transcriptional regulation of genes including\n Rhot1<\/jats:italic>\n and\n Trak1<\/jats:italic>\n . In\u00a0vivo, 48\u2010week\u2010old\n Prdx5<\/jats:italic>\n \n \u2212\/\u2212<\/jats:italic>\n <\/jats:sup>\n mice exhibited mitochondrial dysfunction and myonuclear clustering in myofibers, with reduced treadmill performance (\n p<\/jats:italic>\n \u2009<\u20090.05). Muscle regeneration was impaired in\n Prdx5<\/jats:italic>\n \n \u2212\/\u2212<\/jats:italic>\n <\/jats:sup>\n mice, with decreased expression of regeneration and mitochondrial transport markers and increased nuclear clustering in regenerating myofibers (\n p<\/jats:italic>\n \u2009<\u20090.05).\n Prdx3<\/jats:italic>\n \n \u2212\/\u2212<\/jats:italic>\n <\/jats:sup>\n ;\n Prdx5<\/jats:italic>\n \n \u2212\/\u2212<\/jats:italic>\n <\/jats:sup>\n double\u2010knockout mice displayed accelerated muscle aging, including decreased muscle mass and strength, and elevated expression of E3 ligases Atrogin1 and MuRF1 as early as 10\u2009weeks of age (\n p<\/jats:italic>\n \u2009<\u20090.05). These mice also exhibited increased mitochondrial H\n 2<\/jats:sub>\n O\n 2<\/jats:sub>\n production, which upregulated the expression of Atrogin1 and MuRF1 (\n p<\/jats:italic>\n \u2009<\u20090.05).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Our findings reveal a previously unidentified role of PRDX5 in coordinating mitochondrial function and nuclear positioning during myogenesis and muscle regeneration. The combined deficiency of PRDX3 and PRDX5 accelerates muscle aging by exacerbating oxidative stress and mitochondrial dysfunction, suggesting that enhancing their activity may be a promising therapeutic strategy to prevent sarcopenia and age\u2010related muscle degeneration.<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/jcsm.70098","type":"journal-article","created":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T13:34:23Z","timestamp":1761658463000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["PRDX5 Regulates Mitochondrial Function and Nuclear Spreading in Myogenesis and Acts With PRDX3 to Delay Muscle Aging"],"prefix":"10.1002","volume":"16","author":[{"given":"Joonho","family":"Suh","sequence":"first","affiliation":[{"name":"Department of Molecular Genetics, School of Dentistry and Dental Research Institute Seoul National University Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Je\u2010Hyun","family":"Eom","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, School of Dentistry and Dental Research Institute Seoul National University Seoul Republic of Korea"},{"name":"Department of Life Science Dongguk University\u2010Seoul Goyang Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jongmin","family":"Baik","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, School of Dentistry and Dental Research Institute Seoul National University Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wonn","family":"Shim","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, School of Dentistry and Dental Research Institute Seoul National University Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max\u00a0A.","family":"Tischfield","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Neuroscience Rutgers University Piscataway New Jersey USA"},{"name":"Keck Center for Collaborative Neuroscience Rutgers University Piscataway New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun\u00a0Ae","family":"Woo","sequence":"additional","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences, College of Pharmacy Ewha Womans University Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1228-0404","authenticated-orcid":false,"given":"Yun\u2010Sil","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, School of Dentistry and Dental Research Institute Seoul National University Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,28]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-020518-114310"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2014.09.010"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.13153"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2016.127"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1249\/JES.0000000000000101"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/194821"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474-9726.2007.00347.x"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2016.00446"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2009.01.030"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2017.09.055"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a011304"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.11.027"},{"issue":"35","key":"e_1_2_7_14_1","first-page":"E3631","article-title":"Loss of Miro1\u2010Directed Mitochondrial Movement Results in a Novel Murine Model for Neuron Disease","volume":"111","author":"Nguyen T. 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