Age-dependent oxidation and aggregation of ZnT-1: A role for metal catalyzed oxidation?

Biological aging is associated with the oxidation and/or aggregation of a variety of proteins, which may contribute to the age-dependent loss of function. Protein modification can be caused by multiple chemical mechanisms, which may selectively target specific proteins. Here we show that the ZnT-1 isoform of the family of cation diffusion facilitators suffers age-dependent oxidation and covalent aggregation. Parallel in vitro experiments with a plasma membrane-rich fraction and recombinant ZnT-1 suggest that ZnT-1 aggregation may be caused by metal-catalyzed oxidation (MCO). The latter would be consistent with the known propensity of metal-binding proteins to suffer MCO.