Messaoudi, N, Gautier, V, Kthiri, F, Lelandais, G, Mihoub, M, Joseleau-Petit, D, Caldas, T, Bohn, C, Tolosa, L, Rao, G, Tao, K, Landoulsi, A, Bouloc, P and Richarme, G (2013) Global stress response in a prokaryotic model of DJ-1-associated Parkinsonism. J. Bacteriol. 195:1167-78
YajL is the most closely related Escherichia coli homolog of Parkinsonism-associated protein DJ-1, a protein with a yet-undefined function in the oxidative-stress response. YajL protects cells against oxidative-stress-induced protein aggregation and functions as a covalent chaperone for the thiol proteome, including FeS proteins. To clarify the cellular responses to YajL deficiency, transcriptional profiling of the yajL mutant was performed. Compared to the parental strain, the yajL mutant overexpressed genes coding for chaperones, proteases, chemical chaperone transporters, superoxide dismutases, catalases, peroxidases, components of thioredoxin and glutaredoxin systems, iron transporters, ferritins and FeS cluster biogenesis enzymes, DNA repair proteins, RNA chaperones, and small regulatory RNAs. It also overexpressed the RNA polymerase stress sigma factors sigma S (multiple stresses) and sigma 32 (protein stress) and activated the OxyR and SoxRS oxidative-stress transcriptional regulators, which together trigger the global stress response. The yajL mutant also overexpressed genes involved in septation and adopted a shorter and rounder shape characteristic of stressed bacteria. Biochemical experiments showed that this upregulation of many stress genes resulted in increased expression of stress proteins and improved biochemical function. Thus, protein defects resulting from the yajL mutation trigger the onset of a robust and global stress response in a prokaryotic model of DJ-1-associated Parkinsonism.
DNA Repair; DNA, Bacterial/metabolism; Escherichia coli/genetics; Escherichia coli/metabolism; Escherichia coli Proteins/genetics; Escherichia coli Proteins/metabolism; Gene Expression Profiling; Gene Expression Regulation, Bacterial; Heat-Shock Proteins/biosynthesis; Heat-Shock Proteins/genetics; Intracellular Signaling Peptides and Proteins/genetics; Intracellular Signaling Peptides and Proteins/metabolism; Iron/metabolism; Molecular Chaperones/biosynthesis; Molecular Chaperones/genetics; Mutation; Oncogene Proteins/genetics; Oxidation-Reduction; Oxidative Stress/genetics; Parkinsonian Disorders/genetics; Ribosomal Proteins/genetics; Ribosomal Proteins/metabolism
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