Atg2A/B deficiency switches cytoprotective autophagy to non-canonical caspase-8 activation and apoptosis.

ABSTRACT: Autophagosomal membranes are emerging as platforms for various cell survival and death signaling networks beyond autophagy. While autophagy-dependent cell death has been reported in response to a variety of stimuli, the underlying molecular mechanisms remain far from clear. Here, we demonstrate that inhibition of autophagosome completion by Atg2A/B deletion accumulates immature autophagosomal membranes that promote non-canonical caspase-8 activation in response to nutrient starvation via an intracellular death-inducing signaling complex (iDISC). Importantly, iDISC-induced caspase-8 dimerization and activation occurs on accumulated autophagosomal membranes and requires the LC3 conjugation machinery but is independent from the extrinsic pathway of apoptosis. Moreover, we have identified NF-κ

SUBMITTER: Tang Z 

PROVIDER: S-EPMC5686350 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature