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

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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.
Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
Issue Date
2017-11
Language
English
Article Type
Article
Keywords

CYCLIC GMP-AMP; INNATE IMMUNE SENSOR; I INTERFERON; CYTOSOLIC DNA; INTRACELLULAR DNA; ADAPTIVE IMMUNITY; ACTIVATION; PROTEIN; VIRUS; CELLS

Citation

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v.493, no.1, pp.737 - 743

ISSN
0006-291X
DOI
10.1016/j.bbrc.2017.08.121
URI
http://hdl.handle.net/10203/226605
Appears in Collection
BS-Journal Papers(저널논문)
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