Supervision

Summary

Lipid droplets (LDs) are dynamic organelles composed of neutral lipids and surrounded by a single phospholipid monolayer. There is growing evidence that dysregulation of lipids is associated with neurodegeneration in pathologies such as Alzheimer's and Parkinson's diseases. However, a protective or deleterious role of LDs is still debated. Recently, it was shown that lipid droplets accumulate in cells in response to endoplasmic reticulum stress (ER) which is induced by impaired folding capacity of proteins. To restore ER homeostasis, Unfolded Protein Response (UPR) pathways (IRE1, ATF6 and PERK) are activated upon accumulation of misfolded proteins. The regulated IRE1-dependent decay (RIDD) is an important pathway required for the mRNA decay of mRNA encoding FATP (Fatty acid transport protein), a central protein in lipid homeostasis that is required for LD formation and photoreceptor survival.

In this proposal, we will evaluate the importance of the RIDD pathway on LD formation and neuron survival in physiological in both Drosophila retina and human neuroblastoma cells lines. Specifically, it will be tested the link between the IRE1/RIDD and lipid metabolism and its impact on neuronal function and survival in these models. The long-term objective of this project is to open therapeutic perspectives in neurodegenerative diseases.