Journal
CELL DEATH AND DIFFERENTIATION
Volume 25, Issue 4, Pages 782-794Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41418-017-0017-z
Keywords
-
Categories
Funding
- NHMRC [461221, 1016647, 1106471]
- NHMRC Peter Doherty Early Career Fellowship [1035502]
- NHMRC Fellowships [1020136, 1063008]
- ARC [130100988, 1601100063]
- Australian Federal Government Postgraduate Award
- Australian National Health and Medical Research Council and [361646]
- Victorian State Government Operational Infrastructure Support Grant
Ask authors/readers for more resources
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-beta (IFN-beta) 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available