Figure 8

The three axes of the UPR in Drosophila brains activated by HTorA^ΔE. HTorA^WT may not induce activation of the UPR in ER. However, HTorA^ΔE may induce activation of the three axes of the UPR signalling pathway by directly binding to HSC3 or by impairing protein trafficking and secretion from the ER that results in ER overload. The amounts of transcripts of the IRE1-dependent spliced Xbp1, AFT4, and ATF6 are consequently increased and initiate transcriptional up-regulation of ER-stress and UPR target genes, including HSC3, Xbp1, components of ERAD, ER chaperone, disulfide bond proteins, oxidative stress response proteins, and ATG8b in Drosophila brains. Consequently, the HTorA^ΔE flies showed an increased susceptibility to oxidative and ER stress and a prolonged UPR activation compared with the HTorA^WT flies.