Endoplasmic Reticulum (ER) stress is a cellular event found misregulated in numerous diseases including osteoporosis, osteoarthritis and inflammatory pathologies. ER stress is also involved in physiological events such as fibroblast differentiation after injuries. Numerous proteins transit through the ER in which they are folded and glycosylated. This organelle is also responsible for the synthesis of lipids and calcium homeostasis. If any of these missions fails, aggregating proteins accumulate and become cytotoxic, leading to devastating pathologies. An adaptive response, known as the Unfolded Protein Response (UPR), normally prevents such accumulation by resolving the stress or ultimately eliminating the cell.
Drosophila is a powerful model organism to study ER stress. Indeed, the UPR is largely conserved between insects and humans. We show how Drosophila genetics and its numerous tools can be easily used to show that both protein aggregation and calcium dyshomeostasis activate the same PERK/ATF4 branch of the UPR to induce both caspase-dependent apoptosis and a JNK-dependent hormonal response that allows tissue homeostasis. Interestingly, this response is tissue-specific.
Disclosure of Interest None declared