{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T03:55:30Z","timestamp":1790740530328,"version":"4.1.0"},"reference-count":29,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2018,9,21]],"date-time":"2018-09-21T00:00:00Z","timestamp":1537488000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100007350","name":"Consejo Nacional de Ciencia y Tecnolog\u00eda","doi-asserted-by":"publisher","award":["CB\u2010166042"],"award-info":[{"award-number":["CB\u2010166042"]}],"id":[{"id":"10.13039\/501100007350","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007350","name":"Consejo Nacional de Ciencia y Tecnolog\u00eda","doi-asserted-by":"publisher","award":["CB252942"],"award-info":[{"award-number":["CB252942"]}],"id":[{"id":"10.13039\/501100007350","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2019,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Non\u2010alcoholic fatty liver disease (NAFLD) encompasses a broad spectrum of histopathological changes ranging from non\u2010inflammatory intracellular fat deposition to non\u2010alcoholic steatohepatitis (NASH), which may progress into hepatic fibrosis, cirrhosis, or hepatocellular carcinoma. Recent data suggest that impaired hepatic cholesterol homeostasis and its accumulation are relevant to the pathogenesis of NAFLD\/NASH. Despite a vital physiological function of cholesterol, mitochondrial dysfunction is an important consequence of dietary\u2010induced hypercholesterolemia and was, subsequently, linked to many pathophysiological conditions. The aim in the current study was to evaluate the morphological and molecular changes of cholesterol overload in mouse liver and particularly, in mitochondria, induced by a high\u2010cholesterol (HC) diet for one month. Histopathological studies revealed microvesicular hepatic steatosis and significantly elevated levels of liver cholesterol and triglycerides leading to impaired liver synthesis. Further, high levels of oxidative stress could be determined in liver tissue as well as primary hepatocyte culture. Transcriptomic changes induced by the HC diet involved disruption in key pathways related to cell death and oxidative stress as well as upregulation of genes related to glutathione homeostasis. Impaired liver function could be associated with a decrease in mitochondrial membrane potential and ATP content and significant alterations in mitochondrial dynamics. We demonstrate that cholesterol overload in the liver leads to mitochondrial changes which may render damaged hepatocytes proliferative and resistant to cell death whereby perpetuating liver damage.<\/jats:p>","DOI":"10.1002\/jcp.27474","type":"journal-article","created":{"date-parts":[[2018,9,22]],"date-time":"2018-09-22T01:13:56Z","timestamp":1537578836000},"page":"7213-7223","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":68,"title":["Cholesterol burden in the liver induces mitochondrial dynamic changes and resistance to apoptosis"],"prefix":"10.1002","volume":"234","author":[{"given":"Mayra","family":"Dom\u00ednguez\u2010P\u00e9rez","sequence":"first","affiliation":[{"name":"Laboratorio de Fisiolog\u00eda Celular, Departamento de Ciencias de la Salud, CBS Universidad Aut\u00f3noma Metropolitana Iztapalapa Mexico City M\u00e9xico"},{"name":"Posgrado en Biolog\u00eda Experimental, DCBS, Universidad Aut\u00f3noma Metropolitana Iztapalapa Mexico City M\u00e9xico"},{"name":"Laboratorio de Gen\u00f3mica de Enfermedades Cardiovasculares, Instituto Nacional de Medicina Gen\u00f3mica Mexico City M\u00e9xico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arturo","family":"Simoni\u2010Nieves","sequence":"additional","affiliation":[{"name":"Laboratorio de Fisiolog\u00eda Celular, Departamento de Ciencias de la Salud, CBS Universidad Aut\u00f3noma Metropolitana Iztapalapa Mexico City M\u00e9xico"},{"name":"Posgrado en Biolog\u00eda Experimental, DCBS, Universidad Aut\u00f3noma Metropolitana Iztapalapa Mexico City M\u00e9xico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Rosales","sequence":"additional","affiliation":[{"name":"Posgrado en Biolog\u00eda Experimental, DCBS, Universidad Aut\u00f3noma Metropolitana Iztapalapa Mexico City M\u00e9xico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Nu\u00f1o\u2010L\u00e1mbarri","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n Traslacional, Fundaci\u00f3n Cl\u00ednica M\u00e9dica Sur Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00f3nica","family":"Rosas\u2010Lemus","sequence":"additional","affiliation":[{"name":"Departamento de Gen\u00e9tica Molecular Instituto de Fisiolog\u00eda Celular, UNAM M\u00e9xico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ver\u00f3nica","family":"Souza","sequence":"additional","affiliation":[{"name":"Laboratorio de Fisiolog\u00eda Celular, Departamento de Ciencias de la Salud, CBS Universidad Aut\u00f3noma Metropolitana Iztapalapa Mexico City M\u00e9xico"},{"name":"Laboratorio de Medicina Experimental, Unidad de Medicina Translacional, Instituto de Investigaciones Biom\u00e9dicas, UNAM\/ Instituto Nacional de Cardiolog\u00eda Ignacio Chavez Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roxana U.","family":"Miranda","sequence":"additional","affiliation":[{"name":"Laboratorio de Fisiolog\u00eda Celular, Departamento de Ciencias de la Salud, CBS Universidad Aut\u00f3noma Metropolitana Iztapalapa Mexico City M\u00e9xico"},{"name":"Laboratorio de Medicina Experimental, Unidad de Medicina Translacional, Instituto de Investigaciones Biom\u00e9dicas, UNAM\/ Instituto Nacional de Cardiolog\u00eda Ignacio Chavez Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leticia","family":"Bucio","sequence":"additional","affiliation":[{"name":"Laboratorio de Fisiolog\u00eda Celular, Departamento de Ciencias de la Salud, CBS Universidad Aut\u00f3noma Metropolitana Iztapalapa Mexico City M\u00e9xico"},{"name":"Laboratorio de Medicina Experimental, Unidad de Medicina Translacional, Instituto de Investigaciones Biom\u00e9dicas, UNAM\/ Instituto Nacional de Cardiolog\u00eda Ignacio Chavez Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvador","family":"Uribe Carvajal","sequence":"additional","affiliation":[{"name":"Departamento de Gen\u00e9tica Molecular Instituto de Fisiolog\u00eda Celular, UNAM M\u00e9xico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens U.","family":"Marquardt","sequence":"additional","affiliation":[{"name":"First Department of Medicine University Medical Center, Johannes Gutenberg University Mainz Mainz Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daekwan","family":"Seo","sequence":"additional","affiliation":[{"name":"Bioinformatics Department, Macrogen Corp Rockville Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis E.","family":"Gomez\u2010Quiroz","sequence":"additional","affiliation":[{"name":"Laboratorio de Fisiolog\u00eda Celular, Departamento de Ciencias de la Salud, CBS Universidad Aut\u00f3noma Metropolitana Iztapalapa Mexico City M\u00e9xico"},{"name":"Laboratorio de Medicina Experimental, Unidad de Medicina Translacional, Instituto de Investigaciones Biom\u00e9dicas, UNAM\/ Instituto Nacional de Cardiolog\u00eda Ignacio Chavez Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0501-7226","authenticated-orcid":false,"given":"Mar\u00eda Concepci\u00f3n","family":"Guti\u00e9rrez\u2010Ruiz","sequence":"additional","affiliation":[{"name":"Laboratorio de Fisiolog\u00eda Celular, Departamento de Ciencias de la Salud, CBS Universidad Aut\u00f3noma Metropolitana Iztapalapa Mexico City M\u00e9xico"},{"name":"Laboratorio de Medicina Experimental, Unidad de Medicina Translacional, Instituto de Investigaciones Biom\u00e9dicas, UNAM\/ Instituto Nacional de Cardiolog\u00eda Ignacio Chavez Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,9,21]]},"reference":[{"key":"e_1_2_7_1_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2015.00040"},{"key":"e_1_2_7_1_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2017.02.024"},{"key":"e_1_2_7_1_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2017.11.016"},{"key":"e_1_2_7_1_5_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2010.12.006"},{"key":"e_1_2_7_1_6_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.22192"},{"key":"e_1_2_7_1_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2013.01.005"},{"key":"e_1_2_7_1_8_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/7960386"},{"key":"e_1_2_7_1_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kft134"},{"key":"e_1_2_7_1_10_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.22024"},{"key":"e_1_2_7_1_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2004.10.001"},{"issue":"1","key":"e_1_2_7_1_12_1","first-page":"117","article-title":"Mitochondrial cholesterol in health and disease","volume":"24","author":"Garcia\u2010Ruiz C.","year":"2009","journal-title":"Histology and Histopathology"},{"key":"e_1_2_7_1_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-804274-8.00029-1"},{"key":"e_1_2_7_1_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2016.07.004"},{"key":"e_1_2_7_1_15_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M707733200"},{"key":"e_1_2_7_1_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2014.12.005"},{"key":"e_1_2_7_1_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-16077-y"},{"key":"e_1_2_7_1_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20701"},{"key":"e_1_2_7_1_19_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v23.i36.6571"},{"key":"e_1_2_7_1_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4402280"},{"key":"e_1_2_7_1_21_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/9209825"},{"issue":"4","key":"e_1_2_7_1_22_1","first-page":"456","article-title":"Cholesterol overload in hepatocytes affects nicotinamide adenine dinucleotide phosphate oxidase (NADPH) activity abrogating hepatocyte growth factor (HGF) induced cellular protection","volume":"151","author":"L\u00f3pez\u2010Reyes A. G.","year":"2015","journal-title":"Gaceta Medica de Mexico"},{"key":"e_1_2_7_1_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2006.07.006"},{"key":"e_1_2_7_1_24_1","doi-asserted-by":"publisher","DOI":"10.2165\/00822942-200605030-00005"},{"key":"e_1_2_7_1_25_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/9895176"},{"key":"e_1_2_7_1_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2014.05.027"},{"key":"e_1_2_7_1_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)36896-6"},{"key":"e_1_2_7_1_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-60761-411-1_7"},{"key":"e_1_2_7_1_29_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M412898200"},{"key":"e_1_2_7_1_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(76)80434-6"}],"container-title":["Journal of Cellular Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcp.27474","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcp.27474","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcp.27474","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcp.27474","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T17:03:25Z","timestamp":1747328605000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcp.27474"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,9,21]]},"references-count":29,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2019,5]]}},"alternative-id":["10.1002\/jcp.27474"],"URL":"https:\/\/doi.org\/10.1002\/jcp.27474","archive":["Portico"],"relation":{},"ISSN":["0021-9541","1097-4652"],"issn-type":[{"value":"0021-9541","type":"print"},{"value":"1097-4652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,9,21]]},"assertion":[{"value":"2018-06-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-09-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-09-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}