title: Mitochondrial glutathione: features, regulation and role in disease.
abstract: BACKGROUND
  Mitochondria are the powerhouse of mammalian cells and the main source of reactive oxygen species (ROS) associated with oxygen consumption. In addition, they also play a strategic role in controlling the fate of cells through regulation of death pathways. Mitochondrial ROS production fulfills a signaling role through regulation of redox pathways, but also contributes to mitochondrial damage in a number of pathological states.
  
  
  METHODS
  Mitochondria are exposed to the constant generation of oxidant species, and yet the organelle remains functional due to the existence of an armamentarium of antioxidant defense systems aimed to repair oxidative damage, of which mitochondrial glutathione (mGSH) is of particular relevance. Thus, the aim of the review is to cover the regulation of mGSH and its role in disease.
  
  
  CONCLUSIONS
  Cumulating evidence over recent years has demonstrated the essential role for mGSH in mitochondrial physiology and disease. Despite its high concentration in the mitochondrial matrix, mitochondria lack the enzymes to synthesize GSH de novo, so that mGSH originates from cytosolic GSH via transport through specific mitochondrial carriers, which exhibit sensitivity to membrane dynamics. Depletion of mGSH sensitizes cells to stimuli leading to oxidative stress such as TNF, hypoxia or amyloid β-peptide, thereby contributing to disease pathogenesis.
  
  
  CONCLUSIONS
  Understanding the regulation of mGSH may provide novel insights to disease pathogenesis and toxicity and the opportunity to design therapeutic targets of intervention in cell death susceptibility and disease. This article is part of a Special Issue entitled Cellular functions of glutathione.
authors.affiliation: Department of Cell Death and Proliferation, IIBB-CSIC, Barcelona, Spain. monmari@clinic.ub.es
authors.forename: Montserrat
authors.initials: M
authors.lastname: Marí
authors.forename: Albert
authors.initials: A
authors.lastname: Morales
authors.forename: Anna
authors.initials: A
authors.lastname: Colell
authors.forename: Carmen
authors.initials: C
authors.lastname: García-Ruiz
authors.forename: Neil
authors.initials: N
authors.lastname: Kaplowitz
authors.forename: José C
authors.initials: JC
authors.lastname: Fernández-Checa
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001692:Biological Transport; D003600:Cytosol / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology
chemical_list: D000975:Antioxidants; D005978:Glutathione