Plant essential oil targets TRPV3 for skin renewal and structural mechanism of action.

Our skin safeguards the body homeostasis for health and also provides psychological consolation in social life. Natural essential oils are widely used for skin maintenance, while the molecular target and mechanism of action remain largely unknown. Here, we report that citronellal, a plant-derived acyclic monoterpene commonly used for personal care, stimulates skin renewal by promoting keratinocyte proliferation through the activation of TRPV3. We further present cryo-EM structures of human TRPV3 in complex with acyclic monoterpenes, including citronellal, citral, linalool and isodihydrolavandulal, determined at resolutions of 3.1-3.6 Å. Our structural and functional analysis unmasks consistent yet subtly different binding modes within the TRPV3 vanilloid site. Our results elucidate that essential oil ligands activate TRPV3 channels by competitively displacing endogenous lipids from the vanilloid site. Together, these findings identify TRPV3 as the molecular target of natural acyclic monoterpenes for skin renewal, and delineate the structural basis of action, thus being instrumental for moving forward skin healthcare.