Is the Mitochondrion a Key Site for Crosstalk between Apoptosis and Autophagy?
Mitochondria are well-known regulators and mediators of apoptosis, for instance serving as the site of release of cytochrome c, which activates caspase 9 and then caspase 3. It is interesting to note that both Atg5 and Bcl-2 mediate many of their effects at the level of the mitochondria, and that the toxicity of the Atg5 cleavage fragment can be abrogated by Bcl-2.Another level of complexity is introduced into this cross-talk, since the major pathway for mitochondrial clearance is via autophagy. Indeed, levels of mitochondria accumulate when autophagy is blocked, while mitochondrial load decreases when autophagy is activated. Cells show increased susceptibility to subsequent propapoptotic insults after autophagy is blocked.30, 31 Conversely, after autophagy is induced in cells (or flies), cells show increased resistance to subsequent proapoptotic insults.30 Our data suggest that this is likely to be due to the changes in mitochondrial load resulting from perturbation of autophagy.30 Wh
