TRPM8 channels control Golgi morphology through an AR-dependent induction of the Scd1 gene and modulation of unsaturated lipid content

ABSTRACT Transient receptor potential melastatin 8 (TRPM8), the cold and menthol receptor is essential to thermosensation, although its roles in organs within the body are still unclear. Besides TRPM8, we previously cloned several isoforms, like 4TM-TRPM8, which can be expressed with or without TRPM8. In this study, we characterize the human TRPM8(85) in ER membranes in the vicinity of Golgi apparatus (GA) and mitochondria in prostate epithelial cells. Silencing of TRPM8(85) induces lipid droplet accumulation, GA expansion and fragmentation associated with a drop in the vesicular trafficking to plasmalemma. Furthermore, lipidomic analysis reveals a strong shift in unsaturated fatty acids (UFAs), induced by TRPM8(85) silencing and to a lesser extent silencing of TRPM8. UFAs increase is caused by the induction of Δ9 stearoyl desaturase ( Scd1 ) gene. Silencing SCD1 or palmitate incubation prevent GA expansion in TRPM8(85)-silenced cells. Finally, we demonstrated that TRPM8 regulates SCD1 via the androgen receptor.