Given the predominantly cytoprotect

Given the predominantly cytoprotective role of autophagy, it seems (teleo)logical that induction of apoptosis would be coupled to the inactivation of autophagy (Figure 6C). There are some examples of molecular events that support this concept. Caspase-3 cleaves Beclin 1, thereby destroying its proautophagic activity. The C-terminal fragment of Beclin 1 that results from this cleavage acquires a new function and can amplify mitochondrion-mediated apoptosis (Wirawan et al., 2010). Caspase-3 activation also cleaves and activates Atg4D, an enzyme that catalyzes the delipidation of the LC3 paralog GABARPL1. This proteolytic activation increases Atg4D targeting to mitochondria via a putative BH3 domain and enhances its cytotoxic activity (Betin and Lane, 2009). Similarly, the proteolytic activity of calpain can destroy the proautophagic function of Atg5 (Xia et al., 2010) while it generates an Atg5-derived proapoptotic mitochondrion-permeabilizing fragment of Atg5 (Yousefi et al., 2006).All these results underscore that concept that autophagy and apoptosis are antagonistic events that tend to inhibit each other.