{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:33:42Z","timestamp":1781105622928,"version":"3.54.1"},"reference-count":42,"publisher":"National Academy of Sciences","issue":"49","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2011,12,6]]},"abstract":"<jats:p>\n                    Deficiencies of subunits of the transcriptional regulatory complex Mediator generally result in embryonic lethality, precluding study of its physiological function. Here we describe a missense mutation in\n                    <jats:italic>Med30<\/jats:italic>\n                    causing progressive cardiomyopathy in homozygous mice that, although viable during lactation, show precipitous lethality 2\u20133 wk after weaning. Expression profiling reveals pleiotropic changes in transcription of cardiac genes required for oxidative phosphorylation and mitochondrial integrity. Weaning mice to a ketogenic diet extends viability to 8.5 wk. Thus, we establish a mechanistic connection between Mediator and induction of a metabolic program for oxidative phosphorylation and fatty acid oxidation, in which lethal cardiomyopathy is mitigated by dietary intervention.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1117835108","type":"journal-article","created":{"date-parts":[[2011,11,22]],"date-time":"2011-11-22T02:22:31Z","timestamp":1321928551000},"page":"19678-19682","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":56,"title":["Lethal mitochondrial cardiomyopathy in a hypomorphic\n                    <i>Med30<\/i>\n                    mouse mutant is ameliorated by ketogenic diet"],"prefix":"10.1073","volume":"108","author":[{"given":"Philippe","family":"Krebs","sequence":"first","affiliation":[{"name":"Department of Genetics and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwei","family":"Fan","sequence":"additional","affiliation":[{"name":"The Salk Institute, Howard Hughes Medical Institute, La Jolla, CA 92037;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yen-Hui","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Sciences, Academia Sinica, 11529 Taipei, Taiwan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimimasa","family":"Tobita","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology, Rangos Research Center, Pittsburgh, PA 15201; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Downes","sequence":"additional","affiliation":[{"name":"The Salk Institute, Howard Hughes Medical Institute, La Jolla, CA 92037;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malcolm R.","family":"Wood","sequence":"additional","affiliation":[{"name":"Core Microscopy Facility, The Scripps Research Institute, La Jolla, CA 92037;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Genetics and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Genetics and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Genetics and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Ding","sequence":"additional","affiliation":[{"name":"The Salk Institute, Howard Hughes Medical Institute, La Jolla, CA 92037;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason M.","family":"Spaeth","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, University of Texas Health Science Center, San Antonio, TX 78245"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva Marie Y.","family":"Moresco","sequence":"additional","affiliation":[{"name":"Department of Genetics and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas G.","family":"Boyer","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, University of Texas Health Science Center, San Antonio, TX 78245"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia Wen Ya","family":"Lo","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology, Rangos Research Center, Pittsburgh, PA 15201; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Yen","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Sciences, Academia Sinica, 11529 Taipei, Taiwan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald M.","family":"Evans","sequence":"additional","affiliation":[{"name":"The Salk Institute, Howard Hughes Medical Institute, La Jolla, CA 92037;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce","family":"Beutler","sequence":"additional","affiliation":[{"name":"Department of Genetics and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2011,11,21]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.22.8.2842-2852.2002"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2005.03.011"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2005.03.009"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)80247-6"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1210\/me.2003-0097"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdf348"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.13.18.2365"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0509457102"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01302-06"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1992"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2006.048637"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000103684.77636.CD"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)62023-7"},{"key":"e_1_3_3_14_2","first-page":"371","article-title":"Review: Mitochondrial medicine\u2014Cardiomyopathy caused by defective oxidative phosphorylation","volume":"33","author":"Fosslien E","year":"2003","unstructured":"E Fosslien, Review: Mitochondrial medicine\u2014Cardiomyopathy caused by defective oxidative phosphorylation. Ann Clin Lab Sci 33, 371\u2013395 (2003).","journal-title":"Ann Clin Lab Sci"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000077045.84609.9F"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0403767101"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI10268"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1116"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/331091a0"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81410-5"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2007.03.007"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1180"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.09.024"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1661708"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/85.3.305"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00361.2010"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2008.05460.x"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(03)00391-5"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M402391200"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1005626107"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(02)01967-8"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2007.06.035"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2010.09.021"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI38331"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2008.04.015"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2009.07384.x"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21562"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2010.169"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01889"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(96)64044-0"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0797-226"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2199-11-22"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1117835108","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T20:32:56Z","timestamp":1649795576000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1117835108"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,11,21]]},"references-count":42,"journal-issue":{"issue":"49","published-print":{"date-parts":[[2011,12,6]]}},"alternative-id":["10.1073\/pnas.1117835108"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1117835108","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,11,21]]},"assertion":[{"value":"2011-11-21","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}