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


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-? (IFN-?) 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.

SUBMITTER: Lindqvist LM 

PROVIDER: S-EPMC5864185 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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

Lindqvist Lisa M LM   Frank Daniel D   McArthur Kate K   Dite Toby A TA   Lazarou Michael M   Oakhill Jonathan S JS   Kile Benjamin T BT   Vaux David L DL  

Cell death and differentiation 20171211 4


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 apo  ...[more]

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