Importantly, Zhu et al. has shown that proteasome inhibition activates autophagy through a phosphorylation of eIF2a-dependent mechanism to eliminate protein aggregates and alleviate proteotoxic stress [46] . However, their results also demonstrated that complicated mechanisms are involved in proteasome inhibition-mediated autophagy activation and the phosphorylation of eIF2a only partially accounts for this activation [46] . Thus, it is possible that the complexity of the process may be much higher than presently envisaged, and that other proteins may be as important in controlling autophagy activation as eIF2a.