A complex between Atg7 and caspase-9: a novel mechanism of cross-regulation between autophagy and apoptosis [Cell Biology]
December 20th, 2013 by Han, J., Hou, W., Goldstein, L. A., Stolz, D. B., Watkins, S. C., Rabinowich, H.
Several crosstalk mechanisms between autophagy and apoptosis have been identified, in which certain co-regulators are shared, allowing the same protein to participate in these opposing processes. Our studies suggest that caspase-9 is a novel co-regulator of apoptosis and autophagy, and that its caspase catalytic activity is dispensable for its autophagic role. We provide evidence that caspase-9 facilitates the early events leading to autophagosome formation; that it forms a complex with Atg7; that Atg7 is not a direct substrate for C9 proteolytic activity; and that depending on the cellular context, Atg7 represses the apoptotic capability of C9 while the latter enhances the Atg7-mediated formation of LC3-II. The repression of C9 apoptotic activity is mediated by its direct interaction with Atg7, and it is not related to the autophagic function of Atg7. We propose that the Atg7-caspase-9 complex performs a dual function of linking caspase-9 to the autophagic process while keeping in check its apoptotic activity.