4-hydroxy-2-nonenal and uncoupling proteins: an approach for regulation of mitochondrial ROS production.
One factor that has the potential to regulate reactive oxygen species (ROS) generation is the mild uncoupling of oxidative phosphorylation, i.e. proton (H(+)) leak across the mitochondrial inner membrane. Proton leak has been shown to attenuate ROS generation, whereas ROS and their derivatives (such as superoxide and hydroxynonenal) have been shown to induce H(+) leak through uncoupling proteins (UCPs). This suggests the existence of a feedback loop between ROS and H(+) leak mediated through UCPs. Although the physiological functions of the new UCPs, such as UCP2 and UCP3, are still not established, extensive data support the idea that these mitochondrial carrier proteins are involved in the control of ROS generation. The molecular basis of both ROS generation and hydroxynonenal-induced uncoupling through UCPs is reviewed and the consequences of their interaction for protection against excessive ROS production at the expense of energy production is discussed.
Echtay
Karim S
KS
Department of Biomedical Sciences, Faculty of Medicine and Medical Sciences, University of Balamand, Tripoli, Lebanon. karim.echtay@balamand.edu.lb
Brand
Martin D
MD
D000447:Aldehydes / Q000494:pharmacology*; D004734:Energy Metabolism; D006801:Humans; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000187:drug effects / Q000378:metabolism*; D008954:Models, Biological; D018384:Oxidative Stress / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3
D000447:Aldehydes; D007473:Ion Channels; D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; C000604389:UCP2 protein, human; C000604392:UCP3 protein, human; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3; C027576:4-hydroxy-2-nonenal