1. Academic Validation
  2. Carbonyl cyanide 3-chlorophenylhydrazone (CCCP) suppresses STING-mediated DNA sensing pathway through inducing mitochondrial fission

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.
Dohyeong Kwon 1 Eunbyeol Park 1 Hiromi Sesaki 2 Suk-Jo Kang 3
Affiliations

Affiliations

  • 1 Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea.
  • 2 Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
  • 3 Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea. Electronic address: suk-jo.kang@kaist.ac.kr.
Abstract

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.

Figures
Products