Title: Autophagy induced during apoptosis degrades mitochondria and inhibits type I interferon secretion
Authors: Lindqvist, LM
Frank, D
McArthur, K
Dite, TA
Lazarou, M
Oakhill, JS
Kile, BT
Vaux, DL
Issue Year: 2018
Series Cell Death Differ.:
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.
URI: https://publications.svi.edu.au/publications/4566
Other Identifiers 10.1038/s41418-017-0017-z
Publication type Article