Protein oxidation in response to increased transcriptional or translational errors

作者：Sam Dukan, Anne Farewell, Manuel Ballesteros, François Taddéi, Miroslav Radman, Thomas Nyström · 发表于：Proceedings of the National Academy of Sciences · 年份：2000 · DOI：10.1073/pnas.100422497 · 被引用次数：334 · 研究领域：Redox biology and oxidative stress、Heat shock proteins research、Enzyme Structure and Function

In this study, we show a correlation between synthesis of aberrant proteins and their oxidative modification. The level of aberrant proteins was elevated in Escherichia coli cultures by decreasing transcriptional or translational 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 intracellular oxidative stress remained unchanged, it appears that carbonylation results from the increased susceptibility of the misfolded proteins. These studies show that the cellular protein oxidation is not limited only by available reactive oxygen species, but by the levels of aberrant proteins. Thus, protein oxidation seen in aging cells may be the consequence also of reduced transcriptional/translational fidelity, and protein structures appear to have evolved to minimize oxidative damage. In addition, we discuss the possibility 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.