In the past years, the Italian–German Villa Vigoni conferences have represented a forum discussing redox-regulated reactions that affect human health. The impact of redox regulation by ischemia/reperfusion has been the focus of the ninth conference, held at Loveno di Menaggio, Italy. The fascinating architecture of Villa Vigoni that faces the beautiful Lago di Como in northern Italy, a place known for its tradition in art and science, created an excellent environment to reach out for something vague, known as ‘redox regulation’.

As molecular oxygen is a terminal electron acceptor during oxidative phosphorylation, partial reaction of oxygen with electrons provokes the formation of a variety of reactive oxygen species (ROS), either used for cell signaling or, if the antioxidant capacity is exhausted, for extensive cell damage. Therefore, reduction of O2 is tightly regulated and sources of oxidative stress are under the control of a multifaceted antioxidant defence. In addition, reactive nitrogen species (RNS) have long been implicated as damaging biomolecules, which are considered fundamentally pathogenic in diverse diseases. It is now recognized that redox alterations are not solely mediated through gross damage but also by their discriminating role as redox regulators of cellular signaling. The redox regulators superoxide (O2−) or nitric oxide (NO) are generated by locally and mechanistically defined reactions, which differ according to the physiological stimulus or the pathophysiological condition. The term ‘redox signaling’ describes the regulation of enzymes and mediators by oxidation and subsequent reduction, as part of a signal-transducing network governed by the levels of the pro-oxidant molecules and antioxidant fluxes. However, it is not only the metabolism towards ROS or RNS that accounts for redox regulation, but rather the O2 availability itself contributes in multiple ways. The ability to sense and respond to changes in oxygenation represents a fundamental property to assure the cellular O2 supply to be within a narrow range, which balances the risks of oxidative damage versus oxygen deficiency. A number of issues on redox regulation by ischemia/reperfusion were discussed at the 2006 Villa Vigoni conference.

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