Abstract
Superoxide is considered to be poorly reactive, and cell damage has been attributed to HO· generated via the Haber-Weiss reaction. The function of O2 in this reaction is only to reduce Fe3+ to Fe2+. In vivo, however, superoxide could not out-compete cellular reductants such as glutathione, NADPH, and ascorbate, which makes the observed O2 toxicity rather puzzling. Little attention has been paid to the idea that, irrespective of its poor chemical reactivity, superoxide might be capable of interacting directly with specific intracellular targets; and that even the Haber-Weiss reaction might be a consequence of such direct interactions. This paper summarizes latest data that support the concept of such a mechanism.