Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/121703
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Type: Journal article
Title: Autophagy induced during apoptosis degrades mitochondria and inhibits type i interferon secretion
Author: Lindqvist, L.
Frank, D.
McArthur, K.
Dite, T.
Lazarou, M.
Oakhill, J.
Kile, B.
Vaux, D.
Citation: Cell Death and Differentiation, 2018; 25(4):782-794
Publisher: Nature Publishing Group
Issue Date: 2018
ISSN: 1350-9047
1476-5403
Statement of
Responsibility: 
Lisa M. Lindqvist, Daniel Frank, Kate McArthur, Toby A. Dite, Michael Lazarou, Jonathan S. Oakhill, Benjamin T. Kile, David L. Vaux
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: Mitochondria
Animals
Mice, Knockout
Mice
Interferon Type I
Apoptosis
Autophagy
Apoptosis Regulatory Proteins
AMP-Activated Protein Kinases
Rights: © ADMC Associazione Differenziamento e Morte Cellulare 2017
DOI: 10.1038/s41418-017-0017-z
Grant ID: http://purl.org/au-research/grants/nhmrc/461221
http://purl.org/au-research/grants/nhmrc/1016647
http://purl.org/au-research/grants/nhmrc/1106471
http://purl.org/au-research/grants/nhmrc/361646
http://purl.org/au-research/grants/nhmrc/1020136
http://purl.org/au-research/grants/nhmrc/1063008
http://purl.org/au-research/grants/arc/130100988
http://purl.org/au-research/grants/arc/1601100063
Appears in Collections:Animal and Veterinary Sciences publications
Aurora harvest 8

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