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STING-Mediated Autophagy Is Protective against H2O2-Induced Cell Death

Department of Pharmacology and Therapeutics, University of Melbourne, Parkville, Melbourne 3010, Australia
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2020, 21(19), 7059;
Received: 26 August 2020 / Revised: 19 September 2020 / Accepted: 21 September 2020 / Published: 25 September 2020
(This article belongs to the Special Issue Cell Signaling in Neurodegeneration)
Stimulator of interferon genes (STING)-mediated type-I interferon signaling is a well characterized instigator of the innate immune response following bacterial or viral infections in the periphery. Emerging evidence has recently linked STING to various neuropathological conditions, however, both protective and deleterious effects of the pathway have been reported. Elevated oxidative stress, such as neuroinflammation, is a feature of a number of neuropathologies, therefore, this study investigated the role of the STING pathway in cell death induced by elevated oxidative stress. Here, we report that the H2O2-induced activation of the STING pathway is protective against cell death in wildtype (WT) MEFSV40 cells as compared to STING−/− MEF SV40 cells. This protective effect of STING can be attributed, in part, to an increase in autophagy flux with an increased LC3II/I ratio identified in H2O2-treated WT cells as compared to STING−/− cells. STING−/− cells also exhibited impaired autophagic flux as indicated by p62, LC3-II and LAMP2 accumulation following H2O2 treatment, suggestive of an impairment at the autophagosome-lysosomal fusion step. This indicates a previously unrecognized role for STING in maintaining efficient autophagy flux and protecting against H2O2-induced cell death. This finding supports a multifaceted role for the STING pathway in the underlying cellular mechanisms contributing to the pathogenesis of neurological disorders. View Full-Text
Keywords: STING; interferon; autophagy; oxidative stress STING; interferon; autophagy; oxidative stress
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MDPI and ACS Style

Abdullah, A.; Mobilio, F.; Crack, P.J.; Taylor, J.M. STING-Mediated Autophagy Is Protective against H2O2-Induced Cell Death. Int. J. Mol. Sci. 2020, 21, 7059.

AMA Style

Abdullah A, Mobilio F, Crack PJ, Taylor JM. STING-Mediated Autophagy Is Protective against H2O2-Induced Cell Death. International Journal of Molecular Sciences. 2020; 21(19):7059.

Chicago/Turabian Style

Abdullah, Amar, Frank Mobilio, Peter J. Crack, and Juliet M. Taylor. 2020. "STING-Mediated Autophagy Is Protective against H2O2-Induced Cell Death" International Journal of Molecular Sciences 21, no. 19: 7059.

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