Curcumin targets YAP1 to enhance mitochondrial function and autophagy, protecting against UVB-induced photodamage

Curcumin treatment markedly improved UVB-induced skin lesions and reduced epidermal inflammation and thickness <i>in vivo</i>. <i>In vitro</i>, curcumin intervention alleviated UVB-induced HaCaT cell damage, including reduced viability, increased apoptosis, elevated ROS and DNA damage, and enhanced inflammatory responses. Transcriptomic analysis demonstrated that curcumin upregulated the YAP signaling pathway and mitochondrial autophagy while inhibiting the IL-18 pathway. Further studies revealed that curcumin directly interacts with YAP1, promoting mitochondrial autophagy, an effect blocked by the YAP1 inhibitor Verteporfin. Additionally, curcumin enhances mitochondrial function through YAP1, maintaining mitochondrial integrity and preventing the release of mitochondrial DNA (mtDNA) and mitochondrial ROS (mtROS), thereby suppressing NLRP3/IL-18 pathway activation.