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Background  Dystonia1 (DYT1) dystonia is caused by a glutamic acid deletion (ΔE) mutation in the gene encoding Torsin A in humans (HTorA). To investigate the unknown molecular and cellular mechanisms underlying DYT1 dystonia, we performed an unbiased proteomic analysis.    Results  We found that the amount of proteins and transcripts of an Endoplasmic reticulum (ER) resident chaperone Heat shock protein cognate 3 (HSC3) and a mitochondria chaperone Heat Shock Protein 22 (HSP22) were significantly increased in the HTorA ΔE – expressing brains compared to the normal HTorA (HTorA WT ) expressing brains. The physiological consequences included an increased susceptibility to oxidative and ER stress compared to normal HTorA WT  flies. The alteration of transcripts of Inositol-requiring enzyme-1 (IRE1)-dependent spliced X box binding protein 1(Xbp1), several ER chaperones, a nucleotide exchange factor, Autophagy related protein 8b (ATG8b) and components of the ER associated degradation (ERAD) pathway and increased expression of the Xbp1-enhanced Green Fluorescence Protein (eGFP) in HTorA ΔE  brains strongly indicated the activation of the unfolded protein response (UPR). In addition, perturbed expression of the UPR sensors and inducers in the HTorA ΔE  Drosophila  brains resulted in a significantly reduced life span of the flies. Furthermore, the types and quantities of proteins present in the anti-HSC3 positive microsomes in the HTorA ΔE  brains were different from those of the HTorA WT  brains.    Conclusion  Taken together, these data show that HTorA ΔE  in  Drosophila  brains may activate the UPR and increase the expression of HSP22 to compensate for the toxic effects caused by HTorA ΔE  in the brains.    Electronic supplementary material  The online version of this article (doi:10.1186/s12864-015-1518-0) contains supplementary material, which is available to authorized users.

The pathogenic human Torsin A in Drosophila activates the unfolded protein response and increases susceptibility to oxidative stress