title: Glutathione and mitochondria.
abstract: Glutathione (GSH) is the main non-protein thiol in cells whose functions are dependent on the redox-active thiol of its cysteine moiety that serves as a cofactor for a number of antioxidant and detoxifying enzymes. While synthesized exclusively in the cytosol from its constituent amino acids, GSH is distributed in different compartments, including mitochondria where its concentration in the matrix equals that of the cytosol. This feature and its negative charge at physiological pH imply the existence of specific carriers to import GSH from the cytosol to the mitochondrial matrix, where it plays a key role in defense against respiration-induced reactive oxygen species and in the detoxification of lipid hydroperoxides and electrophiles. Moreover, as mitochondria play a central strategic role in the activation and mode of cell death, mitochondrial GSH has been shown to critically regulate the level of sensitization to secondary hits that induce mitochondrial membrane permeabilization and release of proteins confined in the intermembrane space that once in the cytosol engage the molecular machinery of cell death. In this review, we summarize recent data on the regulation of mitochondrial GSH and its role in cell death and prevalent human diseases, such as cancer, fatty liver disease, and Alzheimer's disease.
authors.affiliation: Department of Cell Death and Proliferation, Institute of Biomedical Research of Barcelona, Consejo Superior de Investigaciones Científicas (IIBB-CSIC) Barcelona, Spain ; Liver Unit, Hospital Clínic, Centre Esther Koplowitz, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)-Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) Barcelona, Spain.
authors.forename: Vicent
authors.initials: V
authors.lastname: Ribas
authors.affiliation: Department of Cell Death and Proliferation, Institute of Biomedical Research of Barcelona, Consejo Superior de Investigaciones Científicas (IIBB-CSIC) Barcelona, Spain ; Liver Unit, Hospital Clínic, Centre Esther Koplowitz, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)-Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) Barcelona, Spain ; Research Center for Alcoholic Liver and Pancreatic Diseases and Cirrhosis, Keck School of Medicine, University of Southern California Los Angeles, CA, USA.
authors.forename: Carmen
authors.initials: C
authors.lastname: García-Ruiz
authors.affiliation: Department of Cell Death and Proliferation, Institute of Biomedical Research of Barcelona, Consejo Superior de Investigaciones Científicas (IIBB-CSIC) Barcelona, Spain ; Liver Unit, Hospital Clínic, Centre Esther Koplowitz, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)-Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) Barcelona, Spain ; Research Center for Alcoholic Liver and Pancreatic Diseases and Cirrhosis, Keck School of Medicine, University of Southern California Los Angeles, CA, USA.
authors.forename: José C
authors.initials: JC
authors.lastname: Fernández-Checa
keywords: Alzheimer disease; cholesterol; glutathione; mitochondria; reactive oxygen species; steatohepatitis