title: Mitochondria in homeostasis of reactive oxygen species in cell, tissues, and organism.
abstract: The recent knowledge on mitochondria as the substantial source of reactive oxygen species, namely superoxide and hydrogen peroxide efflux from mitochondria, is reviewed, as well as nitric oxide and subsequent peroxynitrite generation in mitochondria and their effects. The reactive oxygen species formation in extramitochondrial locations, in peroxisomes, by cytochrome P450, and NADPH oxidase reaction, is also briefly discussed. Conditions are pointed out under which mitochondria represent the major ROS source for the cell: higher percentage of non-phosphorylating and coupled mitochondria, in vivo oxygen levels leading to increased intensity of the reverse electron transport in the respiratory chain, and nitric oxide effects on the redox state of cytochromes. We formulate hypotheses on the crucial role of ROS generated in mitochondria for the whole cell and organism, in concert with extramitochondrial ROS and antioxidant defense. We hypothesize that a sudden decline of mitochondrial ROS production converts cells or their microenvironment into a "ROS sink" represented by the instantly released excessive capacity of ROS-detoxification mechanisms. A partial but immediate decline of mitochondrial ROS production may be triggered by activation of mitochondrial uncoupling, specifically by activation of recruited or constitutively present uncoupling proteins such as UCP2, which may counterbalance the mild oxidative stress.
authors.affiliation: Department of Membrane Transport Biophysics, No. 75, Institute of Physiology, Academy of Sciences of the Czech Republic, Vídenská 1083, CZ 14220 Prague, Czech Republic. jezek@biomed.cas.cz
authors.forename: Petr
authors.initials: P
authors.lastname: Jezek
authors.forename: Lydie
authors.initials: L
authors.lastname: Hlavatá
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D042967:Electron Transport Complex I / Q000378:metabolism; D014450:Electron Transport Complex III / Q000378:metabolism; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D015227:Lipid Peroxidation / Q000502:physiology; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology*; D008954:Models, Biological; D010084:Oxidation-Reduction / Q000187:drug effects; D010085:Oxidative Phosphorylation; D020675:Peroxisomes / Q000502:physiology; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism; D014475:Uncoupling Agents / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D014475:Uncoupling Agents; D013481:Superoxides; D003577:Cytochrome P-450 Enzyme System; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III