A Complex between Atg7 and Caspase-9: A NOVEL MECHANISM OF CROSS-REGULATION BETWEEN AUTOPHAGY AND APOPTOSIS

• Published in: The Journal of biological chemistry Vol. 289; no. 10; pp. 6485 - 6497
• Main Authors: Han, Jie, Hou, Wen, Goldstein, Leslie A, Stolz, Donna B, Watkins, Simon C, Rabinowich, Hannah
• Format: Journal Article
• Language: English
• Published: United States American Society for Biochemistry and Molecular Biology 07-03-2014
• Subjects: Animals; Apoptosis; Autophagy; Autophagy-Related Protein 7; Caspase 9 - genetics; Caspase 9 - metabolism; Cell Line, Tumor; Humans; Mice; Microtubule-Associated Proteins - metabolism; Multienzyme Complexes - genetics; Multienzyme Complexes - metabolism; RNA, Small Interfering - genetics; Signal Transduction; Ubiquitin-Activating Enzymes - genetics; Ubiquitin-Activating Enzymes - metabolism; Caspase; Cellular Regulation; Autophagy; Cell Death; Apoptosis
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M113.536854

Several cross-talk 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 caspase-9 proteolytic activity; and that, depending on the cellular context, Atg7 represses the apoptotic capability of caspase-9, whereas the latter enhances the Atg7-mediated formation of light chain 3-II. The repression of caspase-9 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.