Mitochondrial reactive oxygen species modify extracellular vesicles secretion rate

Extracellular vesicle (EV) secretion rate is stimulated by hypoxia that causes increased reactive oxygen species (ROS) production the mitochondrial electron transport chain (ETC) and hypoxia-induced factor (HIF)-1 signaling; however, their contribution to EV unknown. We found marker in our reporter cell line CD9truc-EGFP was unaffected HIF-1α stabilizer roxadustat; yet, ETC stimulation dichloroacetic acid (DCA) significantly secretion. The DCA-induced blocked antioxidant TEMPO rotenone, an inhibitor of ETC's Complex I. Under hypoxic conditions, limited reduction impedes III. To mimic this, we inhibited III with antimycin A, which ROS-dependent between I accomplished coenzyme Q created mevalonate pathway tyrosine metabolites. Blocking early step using pitavastatin augmented secretion, 4-nitrobenzoate—an condensation metabolites—increased Our findings indicate hypoxia-mimetics targeting modify ROS produced a potent stimulus for