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Autophagy induced during apoptosis degrades mitochondria and inhibits type I interferon secretion
Lindqvist, Lisa M. Frank, Daniel McArthur, Kate Dite, Toby A. Lazarou, Michael Oakhill, Jon Kile, Benjamin T. Vaux, David L.
Lindqvist, Lisa M.
Frank, Daniel
McArthur, Kate
Dite, Toby A.
Lazarou, Michael
Oakhill, Jon
Kile, Benjamin T.
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.
Keywords
Date
2018
Type
Journal article
Journal
Cell Death and Differentiation
Book
Volume
25
Issue
4
Page Range
782-794
Article Number
ACU Department
School of Education
Faculty of Education and Arts
Non-faculty
Faculty of Education and Arts
Non-faculty
Collections
Relation URI
Source URL
Event URL
Open Access Status
License
File Access
Controlled