Abstract 3034 Neurodegeneration: Intra-Lysosomal Lipid Metabolism in the Driver's Seat

Although only 1-3% of the volume of a cell, lysosomes have emerged as critical metabolic and signaling hubs.These membrane-bound compartments degrade macromolecules and clear damaged organelles to enable cellular adaptation to various metabolic states.Lysosomal function is critical for organismal homeostasis-mutations in genes encoding lysosomal proteins cause severe human disorders known as lysosomal storage diseases and lysosomal dysfunction is implicated in age-associated diseases including cancer, metabolic syndrome and neurodegeneration.However, the biochemical basis of the lysosomal dysfunction and how it leads to human diseases remain to be discovered.In my talk, I will present our research focused on elucidating the role of the lysosome in neurodegeneration through decoding lysosomal gene function.This work led to the discovery of novel lipid synthesis, degradation, and transport pathways whose loss causes neurodegenerative diseases, thus providing a foundation for potential therapeutic interventions.