{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T12:40:37Z","timestamp":1791895237453,"version":"4.3.4"},"reference-count":39,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2016,1,13]]},"abstract":"\n Background<\/jats:title>\n \n Mitochondrial reactive oxygen species (\n ROS<\/jats:styled-content>\n ) are associated with metabolic heart disease (\n MHD<\/jats:styled-content>\n ). However, the\u00a0mechanism by which\n ROS<\/jats:styled-content>\n cause\n MHD<\/jats:styled-content>\n is unknown. We tested the hypothesis that mitochondrial\n ROS<\/jats:styled-content>\n are a key mediator of\n MHD<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n Mice fed a high\u2010fat high\u2010sucrose (\n HFHS<\/jats:styled-content>\n ) diet develop\n MHD<\/jats:styled-content>\n with cardiac diastolic and mitochondrial dysfunction that is associated with oxidative posttranslational modifications of cardiac mitochondrial proteins. Transgenic mice that express catalase in mitochondria and wild\u2010type mice were fed an\n HFHS<\/jats:styled-content>\n or control diet for 4\u00a0months. Cardiac mitochondria from\n HFHS<\/jats:styled-content>\n \u2010fed wild\u2010type mice had a 3\u2010fold greater rate of H\n 2<\/jats:sub>\n O\n 2<\/jats:sub>\n production (\n P<\/jats:italic>\n =0.001 versus control diet fed), a 30% decrease in complex\n II<\/jats:styled-content>\n substrate\u2013driven oxygen consumption (\n P<\/jats:italic>\n =0.006), 21% to 23% decreases in complex I and\n II<\/jats:styled-content>\n substrate\u2013driven\n ATP<\/jats:styled-content>\n synthesis (\n P<\/jats:italic>\n =0.01), and a 62% decrease in complex\n II<\/jats:styled-content>\n activity (\n P<\/jats:italic>\n =0.002). In transgenic mice that express catalase in mitochondria, all\n HFHS<\/jats:styled-content>\n diet\u2013induced mitochondrial abnormalities were ameliorated, as were left ventricular hypertrophy and diastolic dysfunction. In\n HFHS<\/jats:styled-content>\n \u2010fed wild\u2010type mice complex\n II<\/jats:styled-content>\n substrate\u2013driven\n ATP<\/jats:styled-content>\n synthesis and activity were restored ex\u00a0vivo by dithiothreitol (5\u00a0mmol\/L), suggesting a role for reversible cysteine oxidative posttranslational modifications. In vitro site\u2010directed mutation of complex\n II<\/jats:styled-content>\n subunit B Cys100 or Cys103 to redox\u2010insensitive serines prevented complex\n II<\/jats:styled-content>\n dysfunction induced by\n ROS<\/jats:styled-content>\n or high glucose\/high palmitate in the medium.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n Mitochondrial\n ROS<\/jats:styled-content>\n are pathogenic in\n MHD<\/jats:styled-content>\n and contribute to mitochondrial dysfunction, at least in part, by causing oxidative posttranslational modifications of complex I and\n II<\/jats:styled-content>\n proteins including reversible oxidative posttranslational modifications of complex\n II<\/jats:styled-content>\n subunit B Cys100 and Cys103.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.115.002555","type":"journal-article","created":{"date-parts":[[2016,1,11]],"date-time":"2016-01-11T22:39:08Z","timestamp":1452551948000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":105,"title":["Mitochondrial Reactive Oxygen Species Mediate Cardiac Structural, Functional, and Mitochondrial Consequences of Diet\u2010Induced Metabolic Heart Disease"],"prefix":"10.1161","volume":"5","author":[{"given":"Aaron L.","family":"Sverdlov","sequence":"first","affiliation":[{"name":"Myocardial Biology Unit, Boston University School of Medicine, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aly","family":"Elezaby","sequence":"additional","affiliation":[{"name":"Myocardial Biology Unit, Boston University School of Medicine, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuzhong","family":"Qin","sequence":"additional","affiliation":[{"name":"Myocardial Biology Unit, Boston University School of Medicine, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica B.","family":"Behring","sequence":"additional","affiliation":[{"name":"Vascular Biology Section, Boston University School of Medicine, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Luptak","sequence":"additional","affiliation":[{"name":"Myocardial Biology Unit, Boston University School of Medicine, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy D.","family":"Calamaras","sequence":"additional","affiliation":[{"name":"Myocardial Biology Unit, Boston University School of Medicine, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah A.","family":"Siwik","sequence":"additional","affiliation":[{"name":"Myocardial Biology Unit, Boston University School of Medicine, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward J.","family":"Miller","sequence":"additional","affiliation":[{"name":"Myocardial Biology Unit, Boston University School of Medicine, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Liesa","sequence":"additional","affiliation":[{"name":"Obesity and Nutrition Section, Mitochondria ARC, Boston University School of Medicine, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orian S.","family":"Shirihai","sequence":"additional","affiliation":[{"name":"Obesity and Nutrition Section, Mitochondria ARC, Boston University School of Medicine, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R.","family":"Pimentel","sequence":"additional","affiliation":[{"name":"Myocardial Biology Unit, Boston University School of Medicine, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A.","family":"Cohen","sequence":"additional","affiliation":[{"name":"Vascular Biology Section, Boston University School of Medicine, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus M.","family":"Bachschmid","sequence":"additional","affiliation":[{"name":"Vascular Biology Section, Boston University School of Medicine, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilson S.","family":"Colucci","sequence":"additional","affiliation":[{"name":"Myocardial Biology Unit, Boston University School of Medicine, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/HHF.0b013e318291329a"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2010.517"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/oby.20520"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2014.06.013"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-014-3171-6"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2014.01.003"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000072789.89096.10"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.111.067801"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2014.07.018"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.13-233445"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1106653"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.113.01744"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1067\/S0894-7317(03)00679-5"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2014.12.001"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.110.003418"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature09787"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.520403"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2011.4336"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.111.246124"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.240242"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.554360"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.2337\/db07-0481"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvr274"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.115.304384"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbabio.2012.12.007"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1079605"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.22.8965"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M702294200"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature13909"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1159\/000117016"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1186\/1752-0509-5-102"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvr071"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.2174\/1381612811319270003"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1681.2009.05274.x"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2015.6311"},{"issue":"2","key":"e_1_3_4_37_2","first-page":"31","article-title":"High energy phosphate of the myocardium: concentration versus free energy change","volume":"82","author":"Kammermeier H","year":"1987","unstructured":"Kammermeier H. High energy phosphate of the myocardium: concentration versus free energy change. Basic Res Cardiol. 1987;82(suppl 2):31\u201336.","journal-title":"Basic Res Cardiol"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00084.2014"},{"key":"e_1_3_4_39_2","first-page":"127","volume-title":"Heart Failure: A Companion to Braunwald's Heart Disease","author":"Sawyer DB","year":"2016","unstructured":"Sawyer DB, Sverdlov AL, Colucci WS. Chapter 8\u2014oxidative stress in heart failure. In: Mann DL, Felker MG, eds. Heart Failure: A Companion to Braunwald's Heart Disease. 3rd ed. Philadelphia: W.B. Saunders; 2016:127\u2013139.","edition":"3"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI37048"}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.115.002555","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T06:49:20Z","timestamp":1715582960000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.115.002555"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,1,13]]},"references-count":39,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2016,1,13]]}},"alternative-id":["10.1161\/JAHA.115.002555"],"URL":"https:\/\/doi.org\/10.1161\/jaha.115.002555","relation":{},"ISSN":["2047-9980"],"issn-type":[{"value":"2047-9980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,1,13]]},"assertion":[{"value":"2015-09-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-11-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-01-11","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e002555"}}