{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T10:42:22Z","timestamp":1782470542354,"version":"3.54.5"},"reference-count":57,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2017,4,13]],"date-time":"2017-04-13T00:00:00Z","timestamp":1492041600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["MOP\u201097869"],"award-info":[{"award-number":["MOP\u201097869"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2017,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Primary ubiquinone (co\u2010enzyme Q) deficiency results in a wide range of clinical features due to mitochondrial dysfunction. Here, we analyse and characterize two mutations in the ubiquinone biosynthetic gene <jats:italic>COQ7<\/jats:italic>. One mutation from the only previously identified patient (V141E), and one (L111P) from a 6\u2010year\u2010old girl who presents with spasticity and bilateral sensorineural hearing loss. We used patient fibroblast cell lines and a heterologous expression system to show that both mutations lead to loss of protein stability and decreased levels of ubiquinone that correlate with the severity of mitochondrial dysfunction. The severity of L111P is enhanced by the particular COQ7 polymorphism (T103M) that the patient carries, but not by a mitochondrial DNA mutation (A1555G) that is also present in the patient and that has been linked to aminoglycoside\u2010dependent hearing loss. We analysed treatment with the unnatural biosynthesis precursor 2,4\u2010dihydroxybenzoate (DHB), which can restore ubiquinone synthesis in cells completely lacking the enzymatic activity of COQ7. We find that the treatment is not beneficial for every <jats:italic>COQ7<\/jats:italic> mutation and its outcome depends on the extent of enzyme activity loss.<\/jats:p>","DOI":"10.1111\/jcmm.13154","type":"journal-article","created":{"date-parts":[[2017,4,14]],"date-time":"2017-04-14T04:08:42Z","timestamp":1492142922000},"page":"2329-2343","source":"Crossref","is-referenced-by-count":67,"title":["Pathogenicity of two <i>COQ7<\/i> mutations and responses to 2,4\u2010dihydroxybenzoate bypass treatment"],"prefix":"10.1111","volume":"21","author":[{"given":"Ying","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Biology McGill University Montr\u00e9al Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Alberta Children's Hospital University of Calgary Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jillian S.","family":"Parboosingh","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Alberta Children's Hospital University of Calgary Calgary Alberta Canada"},{"name":"Alberta Children's Hospital Research Institute for Child and Maternal Health University of Calgary Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aneal","family":"Khan","sequence":"additional","affiliation":[{"name":"Metabolic Diseases Clinic Alberta Children's Hospital University of Calgary Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micheil","family":"Innes","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Alberta Children's Hospital University of Calgary Calgary Alberta Canada"},{"name":"Alberta Children's Hospital Research Institute for Child and Maternal Health University of Calgary Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3592-5711","authenticated-orcid":false,"given":"Siegfried","family":"Hekimi","sequence":"additional","affiliation":[{"name":"Department of Biology McGill University Montr\u00e9al Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,4,13]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2007.02.011"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2003.11.012"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M305034200"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt330"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12368"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.12.048"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2011-100394"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1086\/500092"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI29089"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2007.12.022"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1086\/510023"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2007.12.024"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI45693"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2009.03.018"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2006080833"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2015.133"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.3109\/10409238.2012.741564"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2015-102986"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12742"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms7393"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2001.5977"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/dds530"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1001-0742(08)62350-5"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C000889200"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M108980200"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.360354"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0793-289"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201203090"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.26.10.3976-3985.2006"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0317167100003929"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkg509"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth0410-248"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2890"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C100346200"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2010.03.005"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.37.1.38"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-005-1276-1"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1086\/301676"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1004(1999)13:4<261::AID-HUMU1>3.0.CO;2-W"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19980605)77:5<421::AID-AJMG13>3.0.CO;2-K"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(02)00256-5"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M103686200"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(94)90462-6"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2007.03.007"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2013.12.017"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201404632"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mad.2011.06.009"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005537-200402000-00031"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1097\/AUD.0b013e318047941e"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005537-199704000-00011"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu518"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/5.7.963"},{"key":"e_1_2_7_54_1","first-page":"287432","article-title":"Mitochondrial Sensorineural Hearing Loss: a Retrospective Study and a Description of Cochlear Implantation in a MELAS Patient","volume":"2012","author":"Scarpelli M","year":"2012","journal-title":"Genet Res Int"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0b013e32834ab528"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1002\/biof.155"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(13)70158-3"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2011-301258"}],"container-title":["Journal of Cellular and Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjcmm.13154","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcmm.13154","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T12:54:12Z","timestamp":1696251252000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jcmm.13154"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,4,13]]},"references-count":57,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2017,10]]}},"alternative-id":["10.1111\/jcmm.13154"],"URL":"https:\/\/doi.org\/10.1111\/jcmm.13154","archive":["Portico"],"relation":{},"ISSN":["1582-1838","1582-4934"],"issn-type":[{"value":"1582-1838","type":"print"},{"value":"1582-4934","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,4,13]]}}}