title: A radical shift in perspective: mitochondria as regulators of reactive oxygen species.
abstract: Mitochondria are widely recognized as a source of reactive oxygen species (ROS) in animal cells, where it is assumed that over-production of ROS leads to an overwhelmed antioxidant system and oxidative stress. In this Commentary, we describe a more nuanced model of mitochondrial ROS metabolism, where integration of ROS production with consumption by the mitochondrial antioxidant pathways may lead to the regulation of ROS levels. Superoxide and hydrogen peroxide (H2O2) are the main ROS formed by mitochondria. However, superoxide, a free radical, is converted to the non-radical, membrane-permeant H2O2; consequently, ROS may readily cross cellular compartments. By combining measurements of production and consumption of H2O2, it can be shown that isolated mitochondria can intrinsically approach a steady-state concentration of H2O2in the medium. The central hypothesis here is that mitochondria regulate the concentration of H2O2to a value set by the balance between production and consumption. In this context, the consumers of ROS are not simply a passive safeguard against oxidative stress; instead, they control the established steady-state concentration of H2O2By considering the response of rat skeletal muscle mitochondria to high levels of ADP, we demonstrate that H2O2production by mitochondria is far more sensitive to changes in mitochondrial energetics than is H2O2consumption; this concept is further extended to evaluate how the muscle mitochondrial H2O2balance should respond to changes in aerobic work load. We conclude by considering how differences in the ROS consumption pathways may lead to important distinctions amongst tissues, along with briefly examining implications for differing levels of activity, temperature change and metabolic depression.
authors.affiliation: Department of Biological Sciences, University of Manitoba, Winnipeg, MB, Canada R3T 2N2.|Centre on Aging, University of Manitoba, Winnipeg, MB, Canada R3T 2N2.
authors.forename: Daniel
authors.initials: D
authors.lastname: Munro
authors.affiliation: Department of Biological Sciences, University of Manitoba, Winnipeg, MB, Canada R3T 2N2 jason.treberg@umanitoba.ca.|Centre on Aging, University of Manitoba, Winnipeg, MB, Canada R3T 2N2.|Department of Human Nutritional Sciences, University of Manitoba, Winnipeg, MB, Canada R3T 2N2.
authors.forename: Jason R
authors.identifier: 0000-0001-5112-7325
authors.initials: JR
authors.lastname: Treberg
mesh_terms: D000818:Animals; D004734:Energy Metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism; D018384:Oxidative Stress; D010101:Oxygen Consumption; D017382:Reactive Oxygen Species / Q000378:metabolism*; D064348:Torpor
chemical_list: D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide
keywords: Antioxidant; Energetics; Glutathione peroxidase; Hydrogen peroxide; Oxidative stress; Peroxiredoxin; Skeletal muscle; Thioredoxin