(252f) Vitamin K2 Modulates Mitochondrial Dysfunction Induced By 6-Hydroxydopamine in SH-SY5Y Cells Via Mitochondrial Quality Control Loop

Vitamin K2, a natural fat-soluble vitamin, is a potent neuroprotective molecule owing to its antioxidant effect, but its mechanism has not been fully elucidated. Therefore, we treated SH-SY5Y cells with 6-hydroxydopamine (6-OHDA) in a dose-dependent manner, followed by vitamin K2. 6-OHDA had reduced cell viability, decreased mitochondrial membrane potential, increased the accumulation of reactive oxygen species (ROS), and induced mitochondria-mediated apoptosis and abnormal mitochondrial fission and fusion compared with untreated SH-SY5Y cells. However, vitamin K2 significantly attenuated 6-OHDA-induced changes. Vitamin K2 plays a key role in apoptosis by upregulating and downregulating Bcl-2 and Bax protein expressions, respectively, thereby inhibiting mitochondrial depolarisation and ROS accumulation and maintaining the stability of mitochondrial structure and function. Additionally, vitamin K2 significantly inhibited the 6-OHDA-induced decrease and increase in MFN1/2 and DRP1 expressions, respectively, thereby maintaining the dynamic balance of mitochondrial fusion and fission. Furthermore, vitamin K2 downregulates the expression of p62 and upregulates the expression of LC3A in 6-OHDA-treated cells through the PINK1/Parkin signalling pathway, thereby promoting mitophagy. Moreover, it induced mitochondrial biogenesis in 6-OHDA damaged cells by promoting the expression of PGC-1α, NRF1, and TFAM. These indicate that vitamin K2 can alleviate mitochondrial damage, and that this effect is related to the participation of vitamin K2 in the regulation of the mitochondrial quality control loop, through the maintenance of the mitochondrial quality control system, and repair mitochondrial dysfunction, thereby alleviating neuronal cell death mediated by mitochondrial damage.