A window into lipid peroxyl radicals, peroxidation and electrophilic stress in cells

In this presentation I will describe fluorogenic (off to on) probes we have developed to monitor electron transport,1 lipid peroxidation,2 and electrophilic stress,3 in lipid membranes. I will portray live cell imaging work where we exploit newly developed activatable fluorogenic antioxidants2 and state-of-the-art imaging methodologies to monitor lipid peroxyl radicals under a series of pathological conditions including ferroptosis. Secondly, I will touch upon the ability of cells to detoxify increasing lipid derived electrophile (LDE), exploring the link between lipid hydroperoxide accumulation, LDE formation and cell death. Here, I will describe a recently developed assay (ElectrophileQ) that enables live-cell assessment of the glutathione-mediated LDE conjugation and adduct export steps of the LDE detoxification pathway.3 The body of work provides molecular insight on the onset and progression of a series of conditions, including ferroptosis,2g, 3a where lipid peroxidation and or electrophilic stress are exacerbated.

Speaker: Gonzalo Cosa, McGill University