Fig. 10.

Schematic diagram of signaling pathways involved in AgNPs-induced mitochondrial damage and apoptosis in hippocampal HT22 cells. AgNPs promoted mitochondrial fragmentation via excessive mitochondrial fission/fusion, increased ROS generation, decreased MMP and ATP synthesis, eventually induced mitochondria-dependent apoptosis in HT22 cells. The mechanism was involved in increased Drp1, Fis1, Mfn1, Mfn2 and decreased OPA1 expression, mainly mediated by phosphorylation and mitochondrial translocation of Drp1 Ser616. Furthermore, all aforementioned changes were significantly rescued by NAC and Mdivi-1 except for OPA1 expression, indicating that mechanism of mitochondria-dependent apoptosis in HT22 cells was mediated by excessive activation of ROS-Drp1-mitochondrial fission axis.