Figure 8.

Schematic illustration of the proposed molecular mechanism by which SiNPs induce autophagosome accumulation and aggravate autophagy dysfunction. SiNPs were endocytosed into L-02 cells and stimulated ROS generation. The internalized SiNPs triggered ER stress through the activation of the EIF2AK3 and ATF6 pathways but not the ERN1-XBP1 pathway, along with the upregulation of ATF4 and DDIT3. Then, the 2 factors were translocated to the nucleus and increased the transcriptional expressions of 2 key autophagic genes LC3B and ATG12, contributing to autophagosome formation. Previous study has shown that the internalized SiNPs impaired the lysosomes and inhibited the degradation of the autophagosomes. Therefore, SiNPs induce the autophagosome accumulation and aggravate the autophagy dysfunction.