Protein oxidation in response to increased transcriptional or translational errors

In this study, we show a correlation between synthesis of aberrant proteins and their oxidative modification, The level of aberrant proteins was eleva ted in Escherichia coli cultures by decreasing transcriptional or translati onal fidelity using specific mutations or drugs. Protein carbonylation, an oxidative modification, increased in parallel to the induction of the heat shock chaperone GroEL, As the protein turnover rates and level of intracell ular oxidative stress remained unchanged, it appears that carbonylation res ults from the increased susceptibility of the misfolded proteins, These stu dies show that the cellular protein oxidation is not limited only by availa ble reactive oxygen species, but by the levels of aberrant proteins, Thus, protein oxidation seen in aging cells may be the consequence also of reduce d transcriptional/translational fidelity, and protein structures appear to have evolved to minimize oxidative damage. In addition, we discuss the poss ibility that carbonylation, being an unrepairable protein modification, may serve as a tagging system to shunt misfolded proteins between pathways of refolding by chaperones or the proteolytic apparatus.