Fig. 3.

Interplay between autophagy and apoptosis. BCL-2 sequesters Beclin-1, thereby inhibiting autophagy that can be reversed by BH3 mimetics. Furthermore, Bim can sequester Beclin-1 onto microtubules, which also inhibits autophagy (shown on the left). In contrast, ATG12 conjugation to ATG3 enhances BCL-XL expression, thereby inhibiting apoptosis. Unconjugated ATG12 can act in a manner like BH3-only proteins and induce mitochondrial-dependent apoptosis. Calpain-mediated cleavage of ATG5 results in the liberation of a proapoptotic fragment of ATG5 that leads to mitochondrial outer membrane permeabilisation and cell death. In addition, caspase-mediated cleavage of autophagy proteins inhibits autophagy (shown on the right).