Klotho-mediated changes in the expression of Atg13 alter formation of ULK1 complex and thus initiation of ER- and Golgi-stress response mediated autophagy

In this study, we have performed a detailed step-by-step analysis of autophagy flux-related genes ’ expression and endoplasmic reticulum and Golgi stress related pathways in order to determine the exact mechanistic event when autophagy is inhibited in klotho-deficient cells on account of apoptosis initiation. We provide evidence thatklotho-silencing in LPS-treated cells results in differential course of ER- and Golgi-mediated stress response. Further, we show that inklotho-deficient cells formation of ULK1 complex is inhibited and thus autophagy initiation is blocked on the account of apoptosis activation, while in the control cells cytoprotective autophagy is activated. Finally, inklotho-deficient cells formation of ULK1 complex is prevented by downregulated expression of Atg13. Thus, this study suggests a novel targeting pathway for efficient elimination of autophagy-deficient cells.
Source: Apoptosis - Category: Molecular Biology Source Type: research