| 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 |
| Publisher | NATURE PUBLISHING GROUP |
| 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 |