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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.M. Frank, D. McArthur, K. Dite, T.A. Lazarou, M. Oakhill, J.S. Kile, B.T. Vaux, D.L. |
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 |
Published version: | http://dx.doi.org/10.1038/s41418-017-0017-z |
Appears in Collections: | Animal and Veterinary Sciences publications Aurora harvest 8 |
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