Some of the earliest studies in bioenergetics described a ‘leak’ of electrons from the mitochondrial respiratory chain to oxygen, with the resulting formation of the simple one-electron product, superoxide. Several lines of evidence led to the idea that this process is pathological. For example, formation of superoxide, and its dismutation product hydrogen peroxide, from the mitochondrion was enhanced by mitochondrial poisons and hyperoxia. Since these early beginnings, studies in the redox cell signalling field have shown that these same reactive oxygen species (ROS) and reactive nitrogen species (RNS), such as nitric oxide (NO), serve as signalling molecules in both physiological and pathological situations. These small molecules can act through several mechanisms, including the ability to act as reversible agonists for receptors.

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