{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T14:57:44Z","timestamp":1791557864167,"version":"4.3.4"},"reference-count":129,"publisher":"American Physiological Society","issue":"3","funder":[{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"crossref","award":["grant agreement n. 634413 (EPoS"],"award-info":[{"award-number":["grant agreement n. 634413 (EPoS"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"crossref","award":["European Project on Steatohepatitis)"],"award-info":[{"award-number":["European Project on Steatohepatitis)"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"crossref","award":["77377 (LITMUS"],"award-info":[{"award-number":["77377 (LITMUS"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"crossref","award":["Liver Investigation on Marker Utility in Steatohepatitis)"],"award-info":[{"award-number":["Liver Investigation on Marker Utility in Steatohepatitis)"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["collaborative research center grant DFG CRC 1066\/B3"],"award-info":[{"award-number":["collaborative research center grant DFG CRC 1066\/B3"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["collaborative research center grant CRC 1292\/08"],"award-info":[{"award-number":["collaborative research center grant CRC 1292\/08"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"published-print":{"date-parts":[[2020,9,1]]},"abstract":"<jats:p>Nonalcoholic fatty liver disease (NAFLD) has become the most prevalent liver disease worldwide. NAFLD is tightly linked to the metabolic syndrome, insulin resistance, and oxidative stress. Globally, its inflammatory form, nonalcoholic steatohepatitis (NASH), has become the main cause of liver-related morbidity and mortality, mainly due to liver cirrhosis and primary liver cancer. One hallmark of NASH is the presence of changes in mitochondrial morphology and function that are accompanied by a blocked flow of electrons in the respiratory chain, which increases formation of mitochondrial reactive oxygen species in a self-perpetuating vicious cycle. Consequences are oxidation of DNA bases and mitochondrial DNA depletion that are coupled with genetic and acquired mitochondrial DNA mutations, all impairing the resynthesis of respiratory chain polypeptides. In general, several maladaptations of pathways that usually maintain energy homeostasis occur with the early and late excess metabolic stress in NAFLD and NASH. We discuss the interplay between hepatocyte mitochondrial stress and inflammatory responses, focusing primarily on events initiated and maintained by mitochondrial free radical-induced damage in NAFLD. Importantly, mitochondrial oxidative stress and dysfunction are modulated by key pharmacological targets that are related to excess production of reactive oxygen species, mitochondrial turnover and the mitochondrial unfolded protein response, mitophagy, and mitochondrial biogenesis. However, the efficacy of such interventions depends on NAFLD\/NASH disease stage.<\/jats:p>","DOI":"10.1152\/ajpgi.00121.2020","type":"journal-article","created":{"date-parts":[[2020,6,29]],"date-time":"2020-06-29T14:37:16Z","timestamp":1593441436000},"page":"G400-G411","source":"Crossref","is-referenced-by-count":84,"title":["Mitochondrial oxidative injury: a key player in nonalcoholic fatty liver disease"],"prefix":"10.1152","volume":"319","author":[{"given":"Waleska","family":"Dornas","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Center for Cellular and Molecular Therapy, Universidade Federal de S\u00e3o Paulo, S\u00e3o Paulo, Brazil"},{"name":"Institute of Translational Immunology and Research Center for Immune Therapy, University Medical Center, Johannes Gutenberg University, Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Detlef","family":"Schuppan","sequence":"additional","affiliation":[{"name":"Institute of Translational Immunology and Research Center for Immune Therapy, University Medical Center, Johannes Gutenberg University, Mainz, Germany"},{"name":"Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2012.05.019"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201700001R"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2011.55"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0125617"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexmp.2015.11.008"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aav9701"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1007\/s10541-005-0102-7"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2015.00040"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2002.32028"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2016.09.017"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(94)01290-3"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(95)00763-Y"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(99)80033-6"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2012.04.022"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2003.50095"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0052645"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2013.05.001"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.9.5692"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-4165(98)00002-6"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1002\/iub.1470"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M704213200"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-006-0170-2"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.2001.281.4.G865"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbpb.2005.04.022"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1001\/jama.282.17.1659"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(99)70022-3"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2009.02.019"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(98)70599-2"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2015.04.036"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2017.1280225"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2003.50342"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.9.4820"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.transproceed.2009.09.055"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20973"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2008.08.017"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2012.256"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/S1262-3636(07)70098-8"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00228.2004"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21313"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1002\/hep.28245"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.25.4.1354-1366.2005"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1124\/mol.64.5.1136"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00246.2006"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2019.08.026"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.2337\/db14-1937"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/j.cotox.2016.10.002"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2005.02.001"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2017-315691"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21070"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2135217100"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M701759200"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2015.04.004"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1172\/JCI36066"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0011707"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2014.11.021"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.33549\/physiolres.932022"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.11.013"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1002\/oby.20123"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20177"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20202"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1172\/JCI8814"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.RA118.000961"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2012.08.018"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2018.07.011"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.2337\/diab.46.5.920"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1081\/DMR-200033441"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0630588100"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.3390\/cells9040837"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2018.06.083"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2007.12.029"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20080868"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1038\/nature06261"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20081386"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1159\/000320552"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M901488200"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00022.2011"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2010.3848"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840380426"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa0672"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2005.03.004"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0802917105"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2015.05.014"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2018.1454810"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1515\/BC.2002.044"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(02)01111-5"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1038\/oby.2008.10"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510290428"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2009.11.030"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.2337\/db06-1135"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0536625100"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2001.23256"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.1172\/JCI82204"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00025.2007"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2010.09.019"},{"key":"B95","doi-asserted-by":"crossref","first-page":"5317","DOI":"10.1016\/S0021-9258(18)42768-8","volume":"267","author":"Schulze-Osthoff K","year":"1992","journal-title":"J Biol Chem"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)60383-9"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.12212"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.11.012"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2007.147496"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2362.2008.01936.x"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00247.2014"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2014.10.004"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0611623104"},{"key":"B104","doi-asserted-by":"publisher","DOI":"10.1016\/j.cld.2012.05.011"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.1002\/path.4803"},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M301850200"},{"key":"B107","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(01)00797-3"},{"key":"B108","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2003.049478"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.4067\/S0716-97602008000100010"},{"key":"B110","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2001.23060"},{"key":"B111","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2014-306748"},{"key":"B112","doi-asserted-by":"publisher","DOI":"10.1126\/science.aac4854"},{"key":"B113","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2012.05.024"},{"key":"B114","doi-asserted-by":"publisher","DOI":"10.1126\/science.283.5407.1482"},{"key":"B115","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(96)70028-8"},{"key":"B116","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510270121"},{"key":"B117","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2006.01.001"},{"key":"B118","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21655"},{"key":"B119","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21988"},{"key":"B120","doi-asserted-by":"publisher","DOI":"10.1038\/nm1557"},{"key":"B121","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2001.28054"},{"key":"B122","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.201700261"},{"key":"B123","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2017.109"},{"key":"B124","doi-asserted-by":"publisher","DOI":"10.1101\/gr.078865.108"},{"key":"B125","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1994.74.1.139"},{"key":"B126","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2014.01.011"},{"key":"B127","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2019.101120"},{"key":"B128","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00258.2011"},{"key":"B129","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2013.5538"}],"container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.physiology.org\/doi\/pdf\/10.1152\/ajpgi.00121.2020","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T04:38:33Z","timestamp":1616387913000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.physiology.org\/doi\/10.1152\/ajpgi.00121.2020"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,1]]},"references-count":129,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2020,9,1]]}},"alternative-id":["10.1152\/ajpgi.00121.2020"],"URL":"https:\/\/doi.org\/10.1152\/ajpgi.00121.2020","relation":{},"ISSN":["0193-1857","1522-1547"],"issn-type":[{"value":"0193-1857","type":"print"},{"value":"1522-1547","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,1]]}}}