Cellular and Molecular Biology



Mitochondrial cholesterol in health and disease

Carmen Garcia-Ruiz1, Montserrat Mari1, Anna Colell1, Albert Morales1, Francisco Caballero1, Joan Montero1, Oihana Terrones2, Gorka Basañez2 and José C. Fernández-Checa1,3

1Liver Unit and Centro de Investigaciones Biomédicas Esther Koplowitz, IMDiM, Hospital Clínic i Provincial and CIBEREHD, IDIBAPS, and Department of Cell Death and Proliferation, Instituto Investigaciones Biomédicas de Barcelona, Consejo Superior de Investigaciones Científicas, Barcelona, Spain, 2Unidad de Biofísica (Centro Mixto Consejo Superior Investigaciones Científicas-Universidad del País Vasco/Euskal Herriko Unibersitatea), Universidad del País Vasco/Euskal Herriko Unibersitatea, Bilbao, Spain and 3Research Center for Alcoholic Liver and Pancreatic Diseases, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.

Offprint requests to: J.C. Fernandez-Checa, Liver Unit, Hospital Clinic, IDIBAPS, C/Villarroel, 170, 08036-Barcelona. e-mail: checa229@yahoo.com

Summary. Cholesterol is a critical component of biological membranes, which not only plays an essential role in determining membrane physical properties, but also in the regulation of multiple signaling pathways. Cells satisfy their need for cholesterol either by uptake from nutrients and lipoproteins or de novo synthesis from acetyl-CoA. The latter process occurs in the endoplasmic reticulum, where transcription factors that regulate the expression of enzymes involved in the de novo cholesterol synthesis reside. Cholesterol is distributed to different membranes most prominently to plasma membrane, where it participates in the physical organization of specific membrane domains. Mitochondria, however, 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 step in disease progression, including steatohepatitis, carcinogenesis or Alzheimer disease. Histol Histopathol 24, 117-132 (2009)

Key words: Cholesterol, Mitochondria, Oxidative stress, Glutathione, Membrane dynamics