Redox signaling (cross-talk) from and to mitochondria involves mitochondrial pores and reactive oxygen species.
This review highlights the important role of redox signaling between mitochondria and NADPH oxidases. Besides the definition and general importance of redox signaling, the cross-talk between mitochondrial and Nox-derived reactive oxygen species (ROS) is discussed on the basis of 4 different examples. In the first model, angiotensin-II is discussed as a trigger for NADPH oxidase activation with subsequent ROS-dependent opening of mitochondrial ATP-sensitive potassium channels leading to depolarization of mitochondrial membrane potential followed by mitochondrial ROS formation and respiratory dysfunction. This concept was supported by observations that ethidium bromide-induced mitochondrial damage suppressed angiotensin-II-dependent increase in Nox1 and oxidative stress. In another example hypoxia was used as a stimulator of mitochondrial ROS formation and by using pharmacological and genetic inhibitors, a role of mitochondrial ROS for the induction of NADPH oxidase via PKCvarepsilon was demonstrated. The third model was based on cell death by serum withdrawal that promotes the production of ROS in human 293T cells by stimulating both the mitochondria and Nox1. By superior molecular biological methods the authors showed that mitochondria were responsible for the fast onset of ROS formation followed by a slower but long-lasting oxidative stress condition based on the activation of an NADPH oxidase (Nox1) in response to the fast mitochondrial ROS formation. Finally, a cross-talk between mitochondria and NADPH oxidases (Nox2) was shown in nitroglycerin-induced tolerance involving the mitochondrial permeability transition pore and ATP-sensitive potassium channels. The use of these redox signaling pathways as pharmacological targets is briefly discussed.
Daiber
Andreas
A
Universitätsmedizin der Johannes Gutenberg-Universität Mainz, II. Med. Klinik u. Poliklinik-Labor für Molekulare Kardiologie, Obere Zahlbacher Str. 63, 55101 Mainz, Germany. daiber@uni-mainz.de
D000375:Aging / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D025461:Feedback, Physiological; D006801:Humans; D006973:Hypertension / Q000209:etiology / Q000378:metabolism; D066298:In Vitro Techniques; D008928:Mitochondria / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D008954:Models, Biological; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D015221:Potassium Channels / Q000378:metabolism; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction
D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D015221:Potassium Channels; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; C117780:mitochondrial K(ATP) channel; D000804:Angiotensin II; D019255:NADPH Oxidases