{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T05:37:03Z","timestamp":1775021823381,"version":"3.50.1"},"reference-count":40,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,10,2]],"date-time":"2024-10-02T00:00:00Z","timestamp":1727827200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI20\/00541"],"award-info":[{"award-number":["PI20\/00541"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["CEX2020\u2010001088\u2010M"],"award-info":[{"award-number":["CEX2020\u2010001088\u2010M"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["PID2020\u2010117058GB\u2010I00"],"award-info":[{"award-number":["PID2020\u2010117058GB\u2010I00"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020135","name":"Consejer\u00eda de Igualdad, Pol\u00edticas Sociales y Conciliaci\u00f3n, Junta de Andaluc\u00eda","doi-asserted-by":"publisher","award":["ProyExcel_00153"],"award-info":[{"award-number":["ProyExcel_00153"]}],"id":[{"id":"10.13039\/501100020135","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/P023215\/1"],"award-info":[{"award-number":["MR\/P023215\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/S002472\/1"],"award-info":[{"award-number":["MR\/S002472\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012644","name":"Friends of FSH Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012644","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":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p><jats:italic>ADCK<\/jats:italic> genes\u00a0encode aarF domain\u2010containing mitochondrial kinases involved in coenzyme Q (CoQ) biosynthesis and regulation. Haploinsufficiency of ADCK2 in humans leads to adult\u2010onset physical incapacity with reduced mitochondrial CoQ levels in skeletal muscle, resulting in mitochondrial myopathy and alterations in fatty acid \u03b2\u2010oxidation. The sole current treatment for CoQ deficiencies is oral administration of CoQ<jats:sub>10<\/jats:sub>, which causes only partial recovery with postnatal treatment, underscoring the importance of early diagnosis for successful intervention.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used <jats:italic>Adck2<\/jats:italic> heterozygous mice to examine the influence of this gene on muscle structure, function and regeneration throughout development, growth and ageing. This investigation involved techniques including immunohistochemistry, analysis of CoQ levels, mitochondrial respiratory content, muscle transcriptome analysis and functional tests.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We demonstrated that <jats:italic>Adck2<\/jats:italic> heterozygous mice exhibit defects from embryonic development, particularly in skeletal muscle (1102 genes deregulated). <jats:italic>Adck2<\/jats:italic> heterozygous embryos were 7% smaller in size and displayed signs of delayed development. Prenatal administration of CoQ<jats:sub>10<\/jats:sub> could mitigate these embryonic defects. Heterozygous <jats:italic>Adck2<\/jats:italic> mice also showed a decrease in myogenic cell differentiation, with more severe consequences in \u2018aged\u2019 mice (41.63% smaller) (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01). Consequently, heterozygous <jats:italic>Adck2<\/jats:italic> mice displayed accelerated muscle wasting associated with ageing in muscle structure (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05), muscle function (less grip strength capacity) (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001) and muscle mitochondrial respiration (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001). Furthermore, progressive CoQ<jats:sub>10<\/jats:sub> administration conferred protective effects on mitochondrial function (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.0001) and skeletal muscle (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our work uncovered novel aspects of CoQ deficiencies, revealing defects during embryonic development in mammals for the first time. Additionally, we identified the gradual establishment and progression of the deleterious <jats:italic>Adck2<\/jats:italic> mouse phenotype. Importantly, CoQ<jats:sub>10<\/jats:sub> supplementation demonstrated a protective effect when initiated during development.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.13574","type":"journal-article","created":{"date-parts":[[2024,10,2]],"date-time":"2024-10-02T07:45:25Z","timestamp":1727855125000},"page":"2402-2416","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Prenatal and progressive coenzyme Q<sub>10<\/sub> administration to mitigate muscle dysfunction in mitochondrial disease"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9726-6726","authenticated-orcid":false,"given":"Juan Diego","family":"Hern\u00e1ndez\u2010Camacho","sequence":"first","affiliation":[{"name":"Centro Andaluz de Biolog\u00eda del Desarrollo\u2014CSIC Universidad Pablo de Olavide  Seville Spain"},{"name":"CIBERER Instituto de Salud Carlos III  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7720-9449","authenticated-orcid":false,"given":"Cristina","family":"Vicente\u2010Garc\u00eda","sequence":"additional","affiliation":[{"name":"Centro Andaluz de Biolog\u00eda del Desarrollo\u2014CSIC Universidad Pablo de Olavide  Seville Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorena","family":"Ardila\u2010Garc\u00eda","sequence":"additional","affiliation":[{"name":"Centro Andaluz de Biolog\u00eda del Desarrollo\u2014CSIC Universidad Pablo de Olavide  Seville Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"Padilla\u2010Campos","sequence":"additional","affiliation":[{"name":"Centro Andaluz de Biolog\u00eda del Desarrollo\u2014CSIC Universidad Pablo de Olavide  Seville Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9830-8502","authenticated-orcid":false,"given":"Guillermo","family":"L\u00f3pez\u2010Lluch","sequence":"additional","affiliation":[{"name":"Centro Andaluz de Biolog\u00eda del Desarrollo\u2014CSIC Universidad Pablo de Olavide  Seville Spain"},{"name":"CIBERER Instituto de Salud Carlos III  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2379-796X","authenticated-orcid":false,"given":"Carlos","family":"Santos\u2010Oca\u00f1a","sequence":"additional","affiliation":[{"name":"Centro Andaluz de Biolog\u00eda del Desarrollo\u2014CSIC Universidad Pablo de Olavide  Seville Spain"},{"name":"CIBERER Instituto de Salud Carlos III  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9562-3072","authenticated-orcid":false,"given":"Peter S.","family":"Zammit","sequence":"additional","affiliation":[{"name":"Randall Centre for Cell and Molecular Biophysics King's College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7277-0317","authenticated-orcid":false,"given":"Jaime J.","family":"Carvajal","sequence":"additional","affiliation":[{"name":"Centro Andaluz de Biolog\u00eda del Desarrollo\u2014CSIC Universidad Pablo de Olavide  Seville Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4115-7966","authenticated-orcid":false,"given":"Pl\u00e1cido","family":"Navas","sequence":"additional","affiliation":[{"name":"Centro Andaluz de Biolog\u00eda del Desarrollo\u2014CSIC Universidad Pablo de Olavide  Seville Spain"},{"name":"CIBERER Instituto de Salud Carlos III  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8176-1431","authenticated-orcid":false,"given":"Daniel J.M.","family":"Fern\u00e1ndez\u2010Ayala","sequence":"additional","affiliation":[{"name":"Centro Andaluz de Biolog\u00eda del Desarrollo\u2014CSIC Universidad Pablo de Olavide  Seville Spain"},{"name":"CIBERER Instituto de Salud Carlos III  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,10,2]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2010.04.002"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.10.001"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2017.05.039"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/191144a0"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/biof.1733"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2007.02.006"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-3002(57)90457-2"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2003.11.012"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C100365200"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112222200"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbabio.2010.05.009"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R400007200"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbabio.2010.10.007"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201606356"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00762682"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2017.06.008"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1042\/EBC20170107"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-014-9749-9"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2016.06.007"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000061"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt330"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2016.06.030"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/dds530"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1080\/14737159.2018.1478290"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000150588.75281.58"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm6040037"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc0800582"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-030-70147-5_11"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-25084-7"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25751"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI69000"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm8091374"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2022.898792"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2012-002524"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0035273"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2019"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-1435-7_6"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddy405"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13395-019-0213-2"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12828"}],"container-title":["Journal of Cachexia, Sarcopenia and Muscle"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcsm.13574","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,12]],"date-time":"2024-12-12T02:30:47Z","timestamp":1733970647000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcsm.13574"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,2]]},"references-count":40,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2024,12]]}},"alternative-id":["10.1002\/jcsm.13574"],"URL":"https:\/\/doi.org\/10.1002\/jcsm.13574","archive":["Portico"],"relation":{},"ISSN":["2190-5991","2190-6009"],"issn-type":[{"value":"2190-5991","type":"print"},{"value":"2190-6009","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,2]]},"assertion":[{"value":"2024-03-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-29","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}