Effect of OPA1 loss on expression of genes associated with cellular susceptibility to ferroptosis

OPA1 is a dynamin-related GTPase that plays a critial role in governing mitochondrial fusion, cristae structure, and energetics. Here we found that OPA1 functions as a postive regulator of a nonapoptotic form of cell death termed ferroptosis. Although we determined that the OPA1 GTPase activity is required to drive ferroptosis, the fusogenic activity of OPA1 is dispensable for ferroptosis execution. Mechanistically, our studies show that OPA1 promotes ferroptosis through distinct mechanisms involving the generation of mitochondrial reactive oxygen species and suppression of the integrated stress response. To investigate the effect of OPA1 loss on the transcriptome, we subjected Opa1-/- MEFs and Opa1-/- MEFs reconstituted with OPA1 to RNA sequencing. Comparative gene expression profiling analysis was performed on data from RNA seq.