Open Close
Kim, A.Y., Seo, J.B., Kim, W.T., Choi, H.J., Kim, S.Y., Morrow, G., Tanguay, R.M., Steller, H., Koh, Y.H. (2015). The pathogenic human Torsin A in Drosophila activates the unfolded protein response and increases susceptibility to oxidative stress.  BMC Genomics 16(1): 338.
FlyBase ID
Publication Type
Research paper

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. 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. 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.

PubMed ID
PubMed Central ID
PMC4415242 (PMC) (EuropePMC)
Associated Information
Associated Files
Other Information
Secondary IDs
    Language of Publication
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    BMC Genomics
    BMC Genomics
    Publication Year
    Data From Reference