Figure 11.

UPR- and autophagy-related proteins during ROS accumulation in MCF-7 cells with downregulated RPLP proteins. (A) MCF-7 cells were transduced with the indicated siRNAs (treated as in Fig. 10) and analyzed for the expression of p-EIF2AK3, p-EIF2S1, ATF4, ATF6, and LC3-II conversion. (B) Effect of EIF2AK3 inhibition by treatment with EIF2AK3 inhibitor GSK2606414 (10 μM) on p-EIF2AK3, ATF4, ATF6, LC3, and PARP1 proteins. ACTB was used as a loading control. (C) Proposed model for autophagy activation in stress-related conditions due to RPLP protein deficiency. Black arrows represent the preferred option used by ROS to activate autophagy. In a UPR-defective context, other pathways might operate alternatively to stimulate survival by autophagy (dashed arrows).