The mitochondrial uncoupler FCCP (carbonyl cyanide p-trifluoro methoxyphenylhydrazone) functions as a lipophilic cationic proton translocator that freely carries dissociable protons across membranes and dissipates the proton gradient. This process removes the proton gradient required to drive ATP synthesis. IC50 value is 0.51 μM with treatment of T47D cells against FCCP. [1]?
FCCP is a potent?uncoupler of oxidative phosphorylation?in mitochondria that disrupts ATP synthesis by transporting protons across cell membranes.?
In vitro, FCCP increases the rate of cellular O2 consumption. In PC-3 and DU-145 prostate cancer cells, the compound could significantly decrease hypoxic as well as normoxic HIF-1 transcriptional activity which was in part mediated by down-regulation of the oxygen labile HIF-1α and HIF-2α protein levels. During hypoxic as well as normoxic, it decreases the expression of HIF target genes, VEGF and VEGF receptor-2. [2]?
In vivo, FCCP reduces mitochondrial membrane potential and ATP production in 8-cell mouse embryos. Also, the number of inner cell mass cells decrease within blastocysts with unchanged blastocyst development. This perturbed embryonic mitochondrial function is concomitant with reduced birth weight in female offspring following embryo transfer, which persists until weaning. Although FCCP-treated males also exhibits reduced glucose tolerance as female, their insulin sensitivity and adiposity gain between 4 and 14 weeks is unchanged. Reducing mitochondrial function and, thus, decreasing ATP output in the precompacting embryo can influence offspring phenotype. [3]?
References:
[1]. Du L,?Mahdi F,?Jekabsons MB, et al. Mammea?E/BB, an?isoprenylated?dihydroxycoumarin?protonophore?that?potently?uncouplesmitochondrial?electron? transport,?disrupts?hypoxic?signaling?in?tumor?cells. J Nat Prod.?2010 Nov 29; 73 (11):1868-72.?
[2] Thomas R,?Kim MH. Targeting?the?hypoxia?inducible?factor?pathway?with?mitochondrial?uncouplers. Mol Cell Biochem.?2007 Feb; 296 (1-2):35-44.?
[3] Zander-Fox DL,?Fullston T2,?McPherson NO2, et al. Reduction?of?Mitochondrial?Function?by?FCCP?During?Mouse?Cleavage?Stage?Embryo?Culture Reduces?Birth?Weight?and?Impairs?the?Metabolic?Health?of?Offspring. Biol Reprod.?2015 May; 92 (5):124.
