Format

Send to

Choose Destination
Mol Cell. 2017 Aug 17;67(4):673-684.e8. doi: 10.1016/j.molcel.2017.06.012. Epub 2017 Jul 6.

Activation of the Unfolded Protein Response by Lipid Bilayer Stress.

Author information

1
Institute of Biochemistry and Buchmann Institute for Molecular Life Sciences, Goethe-University, Frankfurt, Max-von-Laue-Strasse 15, 60438 Frankfurt, Germany.
2
Department of Theoretical Biophysics, Max-Planck-Institute of Biophysics, Max-von-Laue-Strasse 3, 60438 Frankfurt, Germany.
3
Institute of Biochemistry, Goethe-University, Frankfurt, Max-von-Laue-Strasse 9, 60438 Frankfurt, Germany.
4
Department of Theoretical Biophysics, Max-Planck-Institute of Biophysics, Max-von-Laue-Strasse 3, 60438 Frankfurt, Germany; Institute of Biophysics, Goethe-University, 60438 Frankfurt, Germany.
5
Institute of Biochemistry and Buchmann Institute for Molecular Life Sciences, Goethe-University, Frankfurt, Max-von-Laue-Strasse 15, 60438 Frankfurt, Germany; Department of Medical Biochemistry and Molecular Biology, Saarland University, 66421 Homburg, Germany. Electronic address: robert.ernst@uks.eu.

Abstract

The unfolded protein response (UPR) is a conserved homeostatic program that is activated by misfolded proteins in the lumen of the endoplasmic reticulum (ER). Recently, it became evident that aberrant lipid compositions of the ER membrane, referred to as lipid bilayer stress, are equally potent in activating the UPR. The underlying molecular mechanism, however, remained unclear. We show that the most conserved transducer of ER stress, Ire1, uses an amphipathic helix (AH) to sense membrane aberrancies and control UPR activity. In vivo and in vitro experiments, together with molecular dynamics (MD) simulations, identify the physicochemical properties of the membrane environment that control Ire1 oligomerization. This work establishes the molecular mechanism of UPR activation by lipid bilayer stress.

KEYWORDS:

ER stress; Ire1; UPR; lipid bilayer stress; membrane quality control; membrane stress; membrane stress response

Comment in

PMID:
28689662
DOI:
10.1016/j.molcel.2017.06.012
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center