Bacterial senescence: protein oxidation in non-proliferating cells is dictated by the accuracy of the ribosomes

We have investigated the causal factors behind the age-related oxidation of proteins during arrest of cell proliferation. A proteomic approach demonst rated that protein oxidation in non-proliferating cells is observed primari ly for proteins being produced in a number of aberrant isoforms. Also, thes e cells exhibited a reduced translational fidelity as demonstrated by both proteomic analysis and genetic measurements of nonsense suppression. Mutant s harboring hyper-accurate ribosomes exhibited a drastically attenuated pro tein oxidation during growth arrest. In contrast, oxidation was augmented i n mutants with error-prone ribosomes. Oxidation increased concomitantly wit h a reduced rate of translation, indicating that the production of aberrant , and oxidized proteins, is not the result of titration of the co-translati onal folding machinery. The age-related accumulation of the chaperones, Dna K and GroEL, was drastically attenuated in the hyperaccurate rpsL mutant, d emonstrating that the reduced translational fidelity in growth-arrested cel ls may also be a primary cause for the induction of the heat shock regulon. The data point to an alternative way of approaching the causal factors inv olved in protein oxidation in eukaryotic G(0) cells.