title: Mitochondrial Cholesterol and the Paradox in Cell Death.
abstract: Mitochondria are considered cholesterol-poor organelles, and obtain their cholesterol load by the action of specialized proteins involved in its delivery from extramitochondrial sources and trafficking within mitochondrial membranes. Although mitochondrial cholesterol fulfills vital physiological functions, such as the synthesis of bile acids in the liver or the formation of steroid hormones in specialized tissues, recent evidence indicates that the accumulation of cholesterol in mitochondria may be a key event in prevalent human diseases, in particular in the development of steatohepatitis (SH) and its progression to hepatocellular carcinoma (HCC). Mitochondrial cholesterol accumulation promotes the transition from simple steatosis to SH due to the sensitization to oxidative stress and cell death. However, mitochondrial cholesterol loading in HCC determines apoptosis resistance and insensitivity to chemotherapy. These opposing functions of mitochondrial cholesterol in SH and HCC define its paradoxical role in cell death as a pro- and anti-apoptotic factor. Further understanding of this conundrum may be useful to modulate the progression from SH to HCC by targeting mitochondrial cholesterol trafficking.
authors.affiliation: Department of Cell Death and Proliferation, Instituto Investigaciones Biomedicas de Barcelona, CSIC, C/Rosello 161, 08036, Barcelona, Spain.|Liver Unit, Hospital Clinic, IDIBAPS, Barcelona, Spain.|Centro de Investigación Biomédica en Red (CIBERehd), Barcelona, Spain.|Keck School of Medicine, USC, University of Southern California Research Center for Alcohol Liver and Pancreatic Diseases and Cirrhosis, Los Angeles, CA, USA.
authors.forename: Carmen
authors.initials: C
authors.lastname: García-Ruiz
authors.affiliation: Department of Cell Death and Proliferation, Instituto Investigaciones Biomedicas de Barcelona, CSIC, C/Rosello 161, 08036, Barcelona, Spain.|Liver Unit, Hospital Clinic, IDIBAPS, Barcelona, Spain.|Centro de Investigación Biomédica en Red (CIBERehd), Barcelona, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Ribas
authors.affiliation: Department of Cell Death and Proliferation, Instituto Investigaciones Biomedicas de Barcelona, CSIC, C/Rosello 161, 08036, Barcelona, Spain.|Liver Unit, Hospital Clinic, IDIBAPS, Barcelona, Spain.|Centro de Investigación Biomédica en Red (CIBERehd), Barcelona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Baulies
authors.affiliation: Department of Cell Death and Proliferation, Instituto Investigaciones Biomedicas de Barcelona, CSIC, C/Rosello 161, 08036, Barcelona, Spain. checa229@yahoo.com.|Liver Unit, Hospital Clinic, IDIBAPS, Barcelona, Spain. checa229@yahoo.com.|Centro de Investigación Biomédica en Red (CIBERehd), Barcelona, Spain. checa229@yahoo.com.|Keck School of Medicine, USC, University of Southern California Research Center for Alcohol Liver and Pancreatic Diseases and Cirrhosis, Los Angeles, CA, USA. checa229@yahoo.com.
authors.forename: Jose C
authors.initials: JC
authors.lastname: Fernández-Checa
mesh_terms: D000818:Animals; D017209:Apoptosis; D001692:Biological Transport; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D005234:Fatty Liver / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology
chemical_list: D002784:Cholesterol; D005978:Glutathione
keywords: Cholesterol; Liver cancer; Mitochondria; Steatohepatitis