Caspase-mediated cleavage of ATG6/Beclin-1 links apoptosis to autophagy in HeLa cells

Autophagy is a catabolic process involved in cell death and in cell protective mechanism. Autophagic cell death is differentiated from apoptosis by the presence of double or multiple-membrane enclosed vesicles, and the ATG proteins are essential for the formation of these autophagic vesicles. Here, we show that ATG6/Beclin-1 is a novel caspase substrate. ATG6 is directly cleaved by caspases in a process inhibited by the pan caspase inhibitor, zVAD. Ectopic expression of ATGG Suppresses cell death while reduction of ATG6 levels by siRNA sensitizes cells to TRAIL-induced cell death. Also, the inhibition of caspases leads to an increase ill autophagy. These results Suggest that caspase-mediated cleavage of ATG6 links the apoptotic and autophagic signaling pathways. (c) 2008 Elsevier Ireland Ltd. All rights reserved.