Activation of the Unfolded Protein Response by Lipid Bilayer Stress (Molecular Cell)

The unfolded protein response (UPR) controls the secretory capacity of a cell and is activated by accumulating unfolded proteins in the lumen of the ER. More recently, it became obvious that aberrant membrane lipid compositions of the ER are equally potent in activating the UPR. Halbleib et al. identify a membrane-based mechanism of UPR activation and establish that Ire1, the most conserved transducer of ER stress, uses an amphipathic helix to sense and respond to aberrant physical properties of the ER membrane.