ER stress protects from retinal degeneration.
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 H(2)O(2), 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.
Mendes
César S
CS
Howard Hughes Medical Institute, The Rockefeller University, New York, NY, USA.
Levet
Clémence
C
Chatelain
Gilles
G
Dourlen
Pierre
P
Fouillet
Antoine
A
Dichtel-Danjoy
Marie-Laure
ML
Gambis
Alexis
A
Ryoo
Hyung Don
HD
Steller
Hermann
H
Mollereau
Bertrand
B