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

Journal article


Lindqvist, Lisa M., Frank, Daniel, McArthur, Kate, Dite, Toby A., Lazarou, Michael, Oakhill, Jon, Kile, Benjamin T. and Vaux, David L.. (2018) Autophagy induced during apoptosis degrades mitochondria and inhibits type I interferon secretion. Cell Death and Differentiation. 25(4), pp. 782 - 794. https://doi.org/10.1038/s41418-017-0017-z
AuthorsLindqvist, Lisa M., Frank, Daniel, McArthur, Kate, Dite, Toby A., Lazarou, Michael, Oakhill, Jon, Kile, Benjamin T. and Vaux, David L.
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.

Year2018
JournalCell Death and Differentiation
Journal citation25 (4), pp. 782 - 794
PublisherNature Publishing Group
ISSN1350-9047
Digital Object Identifier (DOI)https://doi.org/10.1038/s41418-017-0017-z
Scopus EID2-s2.0-85037705823
Page range782 - 794
Research GroupMary MacKillop Institute for Health Research
Publisher's version
File Access Level
Controlled
Place of publicationUnited Kingdom
EditorsG. Melino
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