CCCP can inhibit the activation of STING and is widely used as a protonophore uncoupling agent for oxidative phosphorylation. CCCP is the most commonly used inducer of mitophagy in mammalian cells and is thought to exert its effects by reducing the mitochondrial membrane potential.
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Stimulator of Interferon Genes (STING) is a cytosolic DNA sensing pathway, as a proximal event required for optimal type I interferon production, dendritic cell activation, and priming of CD8+ T cells against tumor-associated antigens[1]. CCCP inhibits IFN-β production induced by various types of the STING pathway activators. CCCP suppresses the phosphorylation of STING, TBK1, and IRF3 via disrupting the association of STING and TBK1. CCCP inhibits activation of STING and its downstream signaling molecules, TBK1 and IRF3, but not STING translocation to the perinuclear region. 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[1]. The same dosage of 3 mg/kg.bw each of CCCP and PPEF is used. In both the cases 1 log reduction is observed in the bacterial load. However, when 3 mg/kg.bw of PPEF is used in combination with 3 mg/kg.bw of CCCP, 6 log10 reduction is observed in the bacterial count. The developed model validates the enhanced antibacterial activity of combination therapy[2]. 99mTc-MIBI signals in the hearts of SD rats administered CCCP (4 mg/kg intraperitoneally) or vehicle is also measured. 99mTc-MIBI signals decrease in rat hearts administered CCCP, and the ATP content, as measured by 31P magnetic resonance spectroscopy, decreased simultaneously. To investigate whether CCCP decreased the 99mTc-MIBI signals in rats, the radioisotope activity of excised heart tissue from rats administered CCCP was analyzed. At 180 min after 99mTc-MIBI injection, the 99mTc-MIBI signals from the hearts in the CCCP group are significantly lower than those in the vehicle group[3]. CCCP is the most commonly used inducer of mitophagy in mammalian cells and is thought to exert its effects by reducing the mitochondrial membrane potential[4].
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