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Article

  • The EMBO Journal (2009) 28, 1296 - 1307
  • doi:10.1038/emboj.2009.76

Published online: 2 April 2009

ER stress protects from retinal degeneration

César S Mendes1,a, Clémence Levet2, Gilles Chatelain2, Pierre Dourlen2, Antoine Fouillet2, Marie-Laure Dichtel-Danjoy2, Alexis Gambis1, Hyung Don Ryoo3, Hermann Steller1 and Bertrand Mollereau2

  1. Howard Hughes Medical Institute, The Rockefeller University, New York, NY, USA
  2. LBMC, UMR5239 CNRS/Ecole Normale Supérieure de Lyon, IFR 128 Biosciences Lyon Gerland, Université de Lyon, Lyon, France
  3. Department of Cell Biology, New York University School of Medicine, New York, NY, USA

Correspondence to:

Bertrand Mollereau, Laboratory of Molecular Biology of the Cell, Ecole Normale Supérieure de Lyon, 9 rue du Vercors, Lyon 69007, France. Tel.: +33 472 728 163; Fax: +33 472 728 674; E-mail: bertrand.mollereau@ens-lyon.fr

aPresent address: Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY, USA

Received 22 September 2008; Accepted 4 March 2009

The unfolded protein response (UPR) is a specific cellular process that allows the cell to cope with the overload of unfolded/misfolded proteins in the endoplasmic reticulum (ER). ER stress is commonly associated with degenerative pathologies, but its role in disease progression is still a matter for debate. Here, we found that mutations in the ER-resident chaperone, neither inactivation nor afterpotential A (NinaA), lead to mild ER stress, protecting photoreceptor neurons from various death stimuli in adult Drosophila. In addition, Drosophila S2 cultured cells, when pre-exposed to mild ER stress, are protected from H2O2, cycloheximide- or ultraviolet-induced cell death. We show that a specific ER-mediated signal promotes antioxidant defences and inhibits caspase-dependent cell death. We propose that an immediate consequence of the UPR not only limits the accumulation of misfolded proteins but also protects tissues from harmful exogenous stresses.

  • Keywords:

    • apoptosis,
    • cyclophilin,
    • Drosophila,
    • photoreceptor neuron,
    • unfolded protein response