Autophagy induced during apoptosis degrades mitochondria and inhibits type I interferon secretion
Details
Publication Year 2018, Volume 25, Issue #4, Page 782-794
Journal Title
Cell Death and Differentiation
Publication Type
Journal Article
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-beta (IFN-beta) 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.
Publisher
Springer Nature
WEHI Research Division(s)
Cell Signalling And Cell Death; Chemical Biology
PubMed ID
29229994
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2018-01-15 09:30:03
Last Modified: 2018-07-09 03:29:57
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