title: Uncoupling proteins and the control of mitochondrial reactive oxygen species production.
abstract: Reactive oxygen species (ROS), natural by-products of aerobic respiration, are important cell signaling molecules, which left unchecked can severely impair cellular functions and induce cell death. Hence, cells have developed a series of systems to keep ROS in the nontoxic range. Uncoupling proteins (UCPs) 1-3 are mitochondrial anion carrier proteins that are purported to play important roles in minimizing ROS emission from the electron transport chain. The function of UCP1 in this regard is highly contentious. However, UCPs 2 and 3 are generally thought to be activated by ROS or ROS by-products to induce proton leak, thus providing a negative feedback loop for mitochondrial ROS production. In our laboratory, we have not only confirmed that ROS activate UCP2 and UCP3, but also demonstrated that UCP2 and UCP3 are controlled by covalent modification by glutathione. Furthermore, the reversible glutathionylation is required to activate/inhibit UCP2 and UCP3, but not UCP1. Hence, our findings are consistent with the notion that UCPs 2 and 3 are acutely activated by ROS, which then directly modulate the glutathionylation status of the UCP to decrease ROS emission and participate in cell signaling mechanisms.
authors.affiliation: Department of Biochemistry, Microbiology, and Immunology, University of Ottawa Faculty of Medicine, Ottawa, ON, Canada K1G8M5.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Mailloux
authors.forename: Mary-Ellen
authors.initials: ME
authors.lastname: Harper
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D025461:Feedback, Physiological; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007473:Ion Channels / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D018384:Oxidative Stress; D011499:Protein Processing, Post-Translational; D017382:Reactive Oxygen Species / Q000378:metabolism; D000071256:Uncoupling Protein 1; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3
chemical_list: D000975:Antioxidants; D007473:Ion Channels; D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; C000604371:UCP1 protein, human; C000604389:UCP2 protein, human; C000604392:UCP3 protein, human; D000071256:Uncoupling Protein 1; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3; D005978:Glutathione