61 Scopus citations

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-? B signaling and c-FLIP as negative regulators of iDISC-mediated caspase-8 activation and apoptosis. Collectively, these findings reveal autophagosomal membrane completion as a novel target to switch cytoprotective autophagy to apoptosis.

Original languageEnglish (US)
Pages (from-to)2127-2138
Number of pages12
JournalCell Death and Differentiation
Volume24
Issue number12
DOIs
StatePublished - Dec 1 2017

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'Atg2A/B deficiency switches cytoprotective autophagy to non-canonical caspase-8 activation and apoptosis'. Together they form a unique fingerprint.

Cite this