Regulation of cell function by methionine oxidation and reduction

Reactive oxygen species (ROS) are generated during normal cellular activity and may exist in excess in some pathophysiological conditions, such as inf lammation or reperfusion injury. These molecules oxidize a variety of cellu lar constituents, but sulfur-containing amino acid residues are especially susceptible. While reversible cysteine oxidation and reduction is part of w ell-established signalling systems, the oxidation and the enzymatically cat alysed reduction of methionine is just emerging as a novel molecular mechan ism for cellular regulation. Here we discuss how the oxidation of methionin e to methionine sulfoxide in signalling proteins such as ion channels affec ts the function of these target proteins. Methionine sulfoxide reductase, w hich reduces methionine sulfoxide to methionine in a thioredoxin-dependent manner, is therefore not only an enzyme important for the repair of age- or degenerative disease-related protein modifications. It is also a potential missing link in the post-translational modification cycle involved in the specific oxidation and reduction of methionine residues in cellular signall ing proteins, which mag give rise to activity-dependent plastic changes in cellular excitability.