Lindqvist, L. M, Frank, D., McArthur, K., Dite, T. A, Lazarou, M., Oakhill, J., Kile, B. T & Vaux, DL. (2018). Autophagy induced during apoptosis degrades mitochondria and inhibits type I interferon secretion. Cell Death and Differentiation,25(4), G. Melino. 782-794. United Kingdom: Nature Publishing Group. Retrieved from https://doi.org/10.1038/s41418-017-0017-z
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.
Mary MacKillop Institute for Health Research
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