title: Mitochondrial glutathione transferases involving a new function for membrane permeability transition pore regulation.
abstract: The mitochondria in mammalian cells are a predominant resource of reactive oxygen species (ROS), which are produced during respiration-coupled oxidative metabolism or various chemical stresses. End-products from membrane-lipid peroxidation caused by ROS are highly toxic, thereby their elimination/scavenging are protective of mitochondria and cells against oxidative damages. In mitochondria, soluble (kappa, alpha, mu, pi, zeta) and membrane-bound glutathione transferases (GSTs) (MGST1) are distributed. Mitochondrial GSTs display both glutathione transferase and peroxidase activities that detoxify such harmful products through glutathione (GSH) conjugation or GSH-mediated peroxide reduction. Some GST isoenzymes are induced by oxidative stress, an adaptation mechanism for the protection of cells from oxidative stress. Membrane-bound MGST1 is activated through the thiol modification in oxidative conditions. Protective action of MGST1 against oxidative stress has been confirmed using MCF7 cells highly expressed of MGST1. In recent years, mitochondria have been recognized as a regulator of cell death via both apoptosis and necrosis, where oxidative stress-induced alteration of the membrane permeability is an important step. Recent studies have shown that MGST1 in the inner mitochondrial membrane could interact with the mitochondrial permeability transition (MPT) regulator proteins, such as adenine nucleotide translocator (ANT) and/or cyclophilin D, and could contribute to oxidant-induced MPT pores. Interaction of GST alpha with ANT has also been shown. In this review, functions of the mitochondrial GSTs, including a new role for mitochondria-mediated cell death, are described.
authors.affiliation: Laboratory of Molecular Genetics and Pharmacology, School of Health Sciences, Faculty of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215, Japan. yaniya@med.u-ryukyu.ac.jp
authors.forename: Yoko
authors.initials: Y
authors.lastname: Aniya
authors.forename: Naoki
authors.initials: N
authors.lastname: Imaizumi
mesh_terms: D000818:Animals; D016923:Cell Death; D005982:Glutathione Transferase / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007425:Intracellular Membranes / Q000201:enzymology / Q000378:metabolism; D007527:Isoenzymes; D008928:Mitochondria / Q000201:enzymology* / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism*; D000083162:Mitochondrial Permeability Transition Pore; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D007527:Isoenzymes; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D017382:Reactive Oxygen Species; D005982:Glutathione Transferase