Rescue of Lipid-Induced Autophagy Inhibition by Torin1 Treatment

Autophagy is an essential cellular process that degrades proteins and organelles and autophagy dysfunction is a hallmark of Parkinson’s disease and Alzheimer’s disease. Therefore, understanding how autophagy is regulated by lipid signaling factors can potentially reveal therapeutic targets for these diseases. Our lab has identified 3 lipids (5-oxo-ete, stearic acid and hydroxystearic acid) that repress autophagy using a lipidomic mass spectrometry screen of serum. RNA sequencing data suggests that mTOR might be affected by these lipids. We have therefore hypothesized that the 3 lipids inhibit autophagy by activating mTOR. To determine if these 3 lipids utilize mTOR for autophagy repression, we will treat differentiated human SH-SY5Y cells (neuron-like cells) with each lipid in the presence or absence of the mTOR inhibitor, Torin 1. Autophagy will then be assessed through examination of LC3-II protein levels by western blot. Our results will add to our understanding of the molecular mechanism of action for these 3 autophagy-repressing lipids which could ultimately aid in the development of treatments for neurodegenerative disease.