Mitochondrial ROS metabolism: modulation by uncoupling proteins.
Most of the oxygen consumed by aerobic organisms is reduced to water by the enzyme cytochrome c oxidase in the terminal reaction of the mitochondrial respiratory chain. A significant proportion of the oxygen molecules are converted to superoxide anion radicals by complexes I and III via a nonenzymatic process. A cascade of enzymes, some of them inside the mitochondria themselves, scavenges superoxide anions in order to protect cells from oxidative damage induced by reactive oxygen species (ROS). Unfortunately, the quantification of the fluxes of mitochondrial ROS inside living cells is currently almost impossible, and this in turn limits our knowledge. Presently, the involvement of mitochondrial ROS can only be demonstrated by indirect strategies and among them knockout techniques are the most convincing. The yield of superoxide generation and subsequently ROS production depend mostly on oxygen concentration but can be efficiently modulated by mitochondrial uncoupling. This role could be assumed in part by one of the Uncoupling Proteins (UCPs). These proteins have coenzyme Q as an obligatory partner and we present here the hypothesis of UCPs as a crucial element of the respiratory chain. ROS have been mostly involved in degenerative processes including ageing. More recently, numerous studies point out the role of ROS as true intracellular second messengers. A putative role of mitochondrial ROS as the sensing element of energy metabolism is discussed here. We propose that UCPs could play a central role in modulation of ROS-dependent signalling pathways and metabolic sensing via the modulation of ROS generation.
Casteilla
L
L
UMR, CNRS UPS 5018, IFR31, CHU Rangueil, Toulouse, France. casteil@rangueil.inscrm.fr
Rigoulet
M
M
Pénicaud
L
L
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D006801:Humans; D007473:Ion Channels; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000378:metabolism*; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism*; D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism; D000071256:Uncoupling Protein 1
D002352:Carrier Proteins; D007473:Ion Channels; D046911:Macromolecular Substances; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; D000071256:Uncoupling Protein 1; D013481:Superoxides