{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T03:22:39Z","timestamp":1789356159708,"version":"build-2803163510"},"reference-count":51,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2011,5,6]],"date-time":"2011-05-06T00:00:00Z","timestamp":1304640000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2011,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      Mitochondrial encephalomyopathy, lactic acidosis, and stroke\u2010like episodes (MELAS) is a mitochondrial disease most usually caused by point mutations in tRNA genes encoded by mtDNA. Here, we report on how this mutation affects mitochondrial function in primary fibroblast cultures established from 2 patients with MELAS who harbored the A3243G mutation. Both mitochondrial respiratory chain enzyme activities and coenzyme Q\n                      <jats:sub>10<\/jats:sub>\n                      (CoQ) levels were significantly decreased in MELAS fibroblasts. A similar decrease in mitochondrial membrane potential was found in intact MELAS fibroblasts. Mitochondrial dysfunction was associated with increased oxidative stress and the activation of mitochondrial permeability transition (MPT), which triggered the degradation of impaired mitochondria. Furthermore, we found defective autophagosome elimination in MELAS fibroblasts. Electron and fluorescence microscopy studies confirmed a massive degradation of mitochondria and accumulation of autophagosomes, suggesting mitophagy activation and deficient autophagic flux. Transmitochondrial cybrids harboring the A3243G mutation also showed CoQ deficiency and increased autophagy activity. All these abnormalities were partially restored by CoQ supplementation. Autophagy in MELAS fibroblasts was also abolished by treatment with antioxidants or cyclosporine, suggesting that both reactive oxygen species and MPT participate in this process. Furthermore, prevention of autophagy in MELAS fibroblasts resulted in apoptotic cell death, suggesting a protective role of autophagy in MELAS fibroblasts.\u2014Cot\u00e1n, D., Cordero, M. D., Garrido\u2010Maraver, J., Oropesa\u2010\u00c1vila, M., Rodr\u00edguez\u2010Hern\u00e1ndez, A., G\u00f3mez Izquierdo, L., De la Mata, M., De Miguel, M., Bautista Lorite, J., Rivas Infante, E., Jackson, S., Navas, P., S\u00e1nchez\u2010Alc\u00e1zar, J. A. Secondary coenzyme Q\n                      <jats:sub>10<\/jats:sub>\n                      deficiency triggers mitochondria degradation by mitophagy in MELAS fibroblasts.\n                      <jats:italic>FASEB J.<\/jats:italic>\n                      25, 2669\u20132687 (2011).\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1096\/fj.10-165340","type":"journal-article","created":{"date-parts":[[2011,5,7]],"date-time":"2011-05-07T00:29:55Z","timestamp":1304728195000},"page":"2669-2687","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":127,"title":["Secondary coenzyme Q\n                    <sub>10<\/sub>\n                    deficiency triggers mitochondria degradation by mitophagy in MELAS fibroblasts"],"prefix":"10.1096","volume":"25","author":[{"given":"David","family":"Cot\u00e1n","sequence":"first","affiliation":[{"name":"Centro Andaluz de Biolog\u00eda del Desarrollo and Centro de Investigaci\u00f3n Biom\u00e9dica en Red: Enfermedades Raras Instituto de Salud Carlos III Universidad Pablo de Olavide\u2010Consejo Superior de Investigaciones Cient\u00edficas Seville Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario D.","family":"Cordero","sequence":"additional","affiliation":[{"name":"Centro Andaluz de Biolog\u00eda del Desarrollo and Centro de Investigaci\u00f3n Biom\u00e9dica en Red: Enfermedades Raras Instituto de Salud Carlos III Universidad Pablo de Olavide\u2010Consejo Superior de Investigaciones Cient\u00edficas Seville Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Garrido\u2010Maraver","sequence":"additional","affiliation":[{"name":"Centro Andaluz de Biolog\u00eda del Desarrollo and Centro de Investigaci\u00f3n Biom\u00e9dica en Red: Enfermedades Raras Instituto de Salud Carlos III Universidad Pablo de Olavide\u2010Consejo Superior de Investigaciones Cient\u00edficas Seville Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Oropesa\u2010Avila","sequence":"additional","affiliation":[{"name":"Centro Andaluz de Biolog\u00eda del Desarrollo and Centro de Investigaci\u00f3n Biom\u00e9dica en Red: Enfermedades Raras Instituto de Salud Carlos III Universidad Pablo de Olavide\u2010Consejo Superior de Investigaciones Cient\u00edficas Seville Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1ngeles","family":"Rodr\u00edguez\u2010Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Centro Andaluz de Biolog\u00eda del Desarrollo and Centro de Investigaci\u00f3n Biom\u00e9dica en Red: Enfermedades Raras Instituto de Salud Carlos III Universidad Pablo de Olavide\u2010Consejo Superior de Investigaciones Cient\u00edficas Seville Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lourdes G\u00f3mez","family":"Izquierdo","sequence":"additional","affiliation":[{"name":"Departamento de Anatom\u00eda Patol\u00f3gica Hospital Virgen del Roc\u00edo Seville Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario De la","family":"Mata","sequence":"additional","affiliation":[{"name":"Centro Andaluz de Biolog\u00eda del Desarrollo and Centro de Investigaci\u00f3n Biom\u00e9dica en Red: Enfermedades Raras Instituto de Salud Carlos III Universidad Pablo de Olavide\u2010Consejo Superior de Investigaciones Cient\u00edficas Seville Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel De","family":"Miguel","sequence":"additional","affiliation":[{"name":"Departamento de Citolog\u00eda e Histolog\u00eda Normal y Patol\u00f3gica Facultad de Medicina Universidad de Sevilla Seville Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Bautista","family":"Lorite","sequence":"additional","affiliation":[{"name":"Hospital del Sagrado Coraz\u00f3n Seville Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eloy Rivas","family":"Infante","sequence":"additional","affiliation":[{"name":"Departamento de Anatom\u00eda Patol\u00f3gica Hospital Virgen del Roc\u00edo Seville Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Jackson","sequence":"additional","affiliation":[{"name":"Department of Neurology Uniklinikum C. G. Carus Dresden Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pl\u00e1cido","family":"Navas","sequence":"additional","affiliation":[{"name":"Centro Andaluz de Biolog\u00eda del Desarrollo and Centro de Investigaci\u00f3n Biom\u00e9dica en Red: Enfermedades Raras Instituto de Salud Carlos III Universidad Pablo de Olavide\u2010Consejo Superior de Investigaciones Cient\u00edficas Seville Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 A.","family":"S\u00e1nchez\u2010Alc\u00e1zar","sequence":"additional","affiliation":[{"name":"Centro Andaluz de Biolog\u00eda del Desarrollo and Centro de Investigaci\u00f3n Biom\u00e9dica en Red: Enfermedades Raras Instituto de Salud Carlos III Universidad Pablo de Olavide\u2010Consejo Superior de Investigaciones Cient\u00edficas Seville Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,5,6]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/290457a0"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1533953"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.19.8739"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0404.2007.00836.x"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/348651a0"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(05)80860-5"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1444.011"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0405173101"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.10.4221"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3180401"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.12.2.480"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2728(92)90226-R"},{"key":"e_1_2_6_14_1","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1096\/fj.04-3045fje","article-title":"Skeletal muscle gene expression profiling in mitochondrial disorders","volume":"19","author":"Crimi M.","year":"2005","journal-title":"FASEB J."},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-006-0301-9"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrfmmm.2005.02.002"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2814477"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2004.031153"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1086\/500092"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/0009-8981(94)90055-8"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)52451-6"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.4161\/auto.5.1.7174"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474-9726.2006.00199.x"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2009.02.006"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2009.10.014"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80450-X"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112222200"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2007.03.034"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2007.07.009"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2007.052076"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2009.08.006"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1327.1999.00066.x"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddn265"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/biof.5520320113"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar2918"},{"key":"e_1_2_6_36_1","first-page":"71","article-title":"Coenzyme q10: is there a clinical role and a case for measurement?","volume":"29","author":"Molyneux S. L.","year":"2008","journal-title":"Clin. Biochem."},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M307841200"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10863-005-6565-9"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-4157(95)00003-A"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1534-5807(04)00099-1"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI26390"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1534-5807(03)00296-X"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1247\/csf.27.409"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/35056522"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2004.10.040"},{"key":"e_1_2_6_46_1","doi-asserted-by":"crossref","first-page":"6699","DOI":"10.1016\/S0021-9258(18)83484-6","article-title":"Energy dependence of different steps in the autophagic\u2010lysosomal pathway","volume":"264","author":"Plomp P. J.","year":"1989","journal-title":"J. Biol. Chem."},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01041376"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-021909-135757"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddm289"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddn174"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.jnen.0000229233.75253.be"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.4161\/auto.1.2.1738"}],"container-title":["The FASEB Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.10-165340","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1096\/fj.10-165340","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.10-165340","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T16:05:11Z","timestamp":1761667511000},"score":1,"resource":{"primary":{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/10.1096\/fj.10-165340"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,5,6]]},"references-count":51,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2011,8]]}},"alternative-id":["10.1096\/fj.10-165340"],"URL":"https:\/\/doi.org\/10.1096\/fj.10-165340","archive":["Portico"],"relation":{},"ISSN":["0892-6638","1530-6860"],"issn-type":[{"value":"0892-6638","type":"print"},{"value":"1530-6860","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,5,6]]},"assertion":[{"value":"2011-04-21","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2011-05-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}