%0 Journal Article
%T Destroy and Exploit: Catalyzed Removal of Hydroperoxides from the Endoplasmic Reticulum
%A Thomas Ramming
%A Christian Appenzeller-Herzog
%J International Journal of Cell Biology
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/180906
%X Peroxidases are enzymes that reduce hydroperoxide substrates. In many cases, hydroperoxide reduction is coupled to the formation of a disulfide bond, which is transferred onto specific acceptor molecules, the so-called reducing substrates. As such, peroxidases control the spatiotemporal distribution of diffusible second messengers such as hydrogen peroxide (H2O2) and generate new disulfides. Members of two families of peroxidases, peroxiredoxins (Prxs) and glutathione peroxidases (GPxs), reside in different subcellular compartments or are secreted from cells. This review discusses the properties and physiological roles of PrxIV, GPx7, and GPx8 in the endoplasmic reticulum (ER) of higher eukaryotic cells where H2O2 and¡ªpossibly¡ªlipid hydroperoxides are regularly produced. Different peroxide sources and reducing substrates for ER peroxidases are critically evaluated. Peroxidase-catalyzed detoxification of hydroperoxides coupled to the productive use of disulfides, for instance, in the ER-associated process of oxidative protein folding, appears to emerge as a common theme. Nonetheless, in vitro and in vivo studies have demonstrated that individual peroxidases serve specific, nonoverlapping roles in ER physiology. 1. Introduction Hydrogen peroxide (H2O2) is an intracellular metabolite, which serves important roles as a second messenger in redox signaling [1]. However, since elevated levels of H2O2 (and of other reactive oxygen species, ROS) can damage proteins, nucleic acids, and lipids by peroxidation, temporal and spatial limitation of H2O2 levels is critically important. Thus, half-life and spatial distribution of H2O2 in the cell are tightly regulated by nonenzymatic antioxidants as well as by specific scavenging enzymes, including the so-called peroxidases of the peroxiredoxin (Prx) or glutathione peroxidase (GPx) families [2]. Prx and GPx isoforms reside in different subcellular compartments where they catalyze the reduction of H2O2 to H2O [2]. The most relevant producers of intracellular ROS/H2O2 are the transmembrane enzyme complexes of the nicotinamide adenine dinucleotide oxidase (NOX) family, various enzymes and the respiratory chain in mitochondria, peroxisomal enzymes, and sulfhydryl oxidases in the endoplasmic reticulum (ER) [3¨C7]. Due to the presence of specific aquaporin channels in cellular membranes, the local diffusion of H2O2 is usually not restricted by organelle boundaries [8, 9]. There are a total of six isoforms of Prx in mammals, all of which form distinct types of antiparallel homooligomers [10]. H2O2-mediated oxidation of the
%U http://www.hindawi.com/journals/ijcb/2013/180906/