Intracellular calcium is a rheostat for the STING signaling pathway
- PMID: 29673589
- DOI: 10.1016/j.bbrc.2018.04.117
Intracellular calcium is a rheostat for the STING signaling pathway
Abstract
Stimulator of IFN genes (STING) is essential for the DNA-sensing innate immune pathway. Recently, evidence is emerging that suggests STING also plays important roles in autoimmunity, cancer therapy, and senescence. Although a multitude of post-translational modifications that regulate the STING pathway have been discovered, the cellular events that guide STING translocation remain unclear. Here, we show, paradoxically, that both BAPTA-AM-mediated calcium depletion and ionomycin-induced calcium elevation suppress STING translocation and STING-mediated IFN-β production. We demonstrate that the mitochondria fission mediator DRP1 is crucial for ionomycin-induced inhibition of IFN-β production. Furthermore, knockout of DRP1 suppressed ionomycin-induced increases in calcium as well as mitochondrial fragmentation. Collectively, our findings reveal that the induction of STING signaling is contingent on a fine-tuning of intracellular calcium levels.
Keywords: Calcium; DRP1; Mitochondria; STING; Type I interferon.
Copyright © 2018 Elsevier Inc. All rights reserved.
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