Autophagy induced during apoptosis degrades mitochondria and inhibits type I interferon secretion

Lisa M. Lindqvist, Daniel Frank, Kate McArthur, Toby A. Dite, Michael Lazarou, Jonathan S. Oakhill, Benjamin T. Kile, David L. Vaux

Research output: Contribution to journalArticleResearchpeer-review

13 Citations (Scopus)

Abstract

Cells undergoing Bax/Bak-mediated apoptosis exhibit signs of autophagy, but how it is activated and its significance is unknown. By directly activating Bax/Bak with BH3-only proteins or BH3 mimetic compounds, we demonstrate that mitochondrial damage correlated with a rapid increase in intracellular [AMP]/[ATP], phosphorylation of 5′ AMP-activated protein kinase (AMPK), and activation of unc-51 like autophagy activating kinase 1 (ULK1). Consequently, autophagic flux was triggered early in the apoptotic pathway, as activation of the apoptosome and caspases were not necessary for its induction. Bax/Bak-triggered autophagy resulted in the clearance of damaged mitochondria in an ATG5/7-dependent manner that did not require Parkin. Importantly, Bax/Bak-mediated autophagy inhibited the secretion of the pro-inflammatory cytokine interferon-β (IFN-β) produced in response to mitochondrial damage, but not another cytokine interleukin-6 (IL-6). These findings show that Bax/Bak stimulated autophagy is essential for ensuring immunological silence during apoptosis.

Original languageEnglish
Pages (from-to)782-794
Number of pages13
JournalCell Death and Differentiation
Volume25
DOIs
Publication statusPublished - 11 Dec 2017

Keywords

  • inflammation
  • macroautophagy

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