Journal article
Autophagy induced during apoptosis degrades mitochondria and inhibits type i interferon secretion
LM Lindqvist, D Frank, K McArthur, TA Dite, M Lazarou, JS Oakhill, BT Kile, DL Vaux
Cell Death and Differentiation | NATURE PUBLISHING GROUP | Published : 2018
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 ..
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Awarded by Australian Research Council
Funding Acknowledgements
We thank J. Bernadini, S. Iyer, I. Tan, and G. Dewson (WEHI) for helpful discussions and technical assistance. S63845 was a kind gift from C. Burns (WEHI). Funding for this project was provided by NHMRC Program Grants 461221 (D.L.V.) and 1016647 (B.T.K.) and Project Grant 1106471 (M.L.). L.M.L. was supported by an NHMRC Peter Doherty Early Career Fellowship 1035502, and D.L.V. and B.T.K. held NHMRC Fellowships (1020136 and 1063008, respectively). J.S.O. (130100988) and M.L. (1601100063) are ARC Future Fellows and K.M. is supported by an Australian Federal Government Postgraduate Award. This work was made possible through Independent Research Institutes Infrastructure Support Scheme Grant (361646) from the Australian National Health and Medical Research Council and a Victorian State Government Operational Infrastructure Support Grant.