Carbonyl cyanide 3-chlorophenylhydrazone (CCCP) suppresses STING-mediated DNA sensing pathway through inducing mitochondrial fission

Biochem Biophys Res Commun. 2017 Nov 4;493(1):737-743. doi: 10.1016/j.bbrc.2017.08.121. Epub 2017 Aug 30.


Besides its important role in innate immune response to DNA virus infection, the regulatory function of STING in autoimmunity and cancer is emerging. Recently, multiple mechanisms regulating the activity of the STING pathway have been revealed. Previous study showed that carbonyl cyanide 3-chlorophenylhydrazone (CCCP), the protonophore, inhibited STING-mediated IFN-β production via disrupting mitochondrial membrane potential (MMP). However, how MMP dissipation leads to the suppression of the STING pathway remains unknown. Here, we show that CCCP inhibits activation of STING and its downstream signaling molecules, TBK1 and IRF3, but not STING translocation to the perinuclear region. We found that CCCP impairs the interaction between STING and TBK1 and concomitantly triggers mitochondria fission. Importantly, the knockout of the crucial mitochondria fission regulator Drp1 restored the STING activity, indicating that CCCP down-modulates the STING pathway through DRP1-mediated mitochondria fragmentation. Our findings highlight the coupling of the STING signaling platform to mitochondria dynamics.

Keywords: CCCP; DRP1; IFN-β; Mitochondrial dynamics; STING; TBK1.

MeSH terms

  • Animals
  • DNA / metabolism*
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Hydrazones / administration & dosage*
  • Membrane Potential, Mitochondrial / drug effects
  • Membrane Potential, Mitochondrial / physiology*
  • Membrane Proteins / metabolism*
  • Mice
  • Mitochondrial Dynamics / drug effects*
  • Mitochondrial Dynamics / physiology*
  • RAW 264.7 Cells
  • Signal Transduction / drug effects
  • Signal Transduction / physiology


  • Hydrazones
  • Membrane Proteins
  • STING1 protein, human
  • carbonyl 3-chlorophenylhydrazone
  • DNA