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

Lindqvist, LM; Frank, D; McArthur, K; Dite, TA; Lazarou, M; Oakhill, JS; Kile, BT; Vaux, DL

Author(s): Lindqvist, LM; Frank, D; McArthur, K; Dite, TA; Lazarou, M; Oakhill, JS; Kile, BT; Vaux, DL;
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
Research Division(s): Cell Signalling And Cell Death; Chemical Biology
PubMed ID: 29229994
Publisher's Version: https://doi.org/10.1038/s41418-017-0017-z
Terms of Use/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