Intracellular calcium is a rheostat for the STING signaling pathway

Biochem Biophys Res Commun. 2018 Jun 2;500(2):497-503. doi: 10.1016/j.bbrc.2018.04.117. Epub 2018 Apr 21.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Dynamins / deficiency
  • Dynamins / metabolism
  • Egtazic Acid / analogs & derivatives
  • Egtazic Acid / pharmacology
  • Embryo, Mammalian / cytology
  • Fibroblasts / metabolism
  • Interferon-beta / biosynthesis
  • Intracellular Space / metabolism*
  • Ionomycin / pharmacology
  • Membrane Proteins / metabolism*
  • Mice
  • RAW 264.7 Cells
  • Signal Transduction*


  • Membrane Proteins
  • Sting1 protein, mouse
  • 1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester
  • Egtazic Acid
  • Ionomycin
  • Interferon-beta
  • Dnm1l protein, mouse
  • Dynamins
  • Calcium