Augmentation of Phospholipid Concentrations and Lipid Raft Signaling in SDHB Knockdown Cells After SCD1 Silencing

Pheochromocytoma and paraganglioma (PPGL) patients with pathogenic variants in the succinate dehydrogenase B subunit (SDHB) frequently develop aggressive disease with poor prognosis. The stearoyl-CoA desaturase 1 (SCD1) protein plays an important role in lipid metabolism. Here, we hypothesized siRNA mediated knockdown of SCD1 compared to non-targeting siRNA would alter the lipid composition of extracellular vesicles (EVs) released from SDHB KD cells compared to hPheo1wild-type (WT) progenitor cells and augment lipid raft density in recipient cells. Quantitative polymerase chain reaction showed that SDHB KD cells expressed less SCD1 than hPheo1 WT cells. The concentration of total phospholipids was greater in SDHB KD cells compared to hPheo1 WT cells, while siRNA-mediated knockdown of SCD1 resulted in decreased concentration in both cell types. Conditioned media EVs increased lipid raft density in recipient cells, which was blunted after SCD1 knockdown. These data suggest there are differences in the phospholipid composition between hPheo1 WT and SDHB KD cells and that EVs released from both cell types have the potential to activate lipid raft signaling pathways, which can be blocked by suppressing SCD1. Further research is necessary to investigate the mechanism of SCD1 inhibitors in SDHB-mutated PPGL.