FCCP

FCCP is a mitochondrial uncoupling agent, used in cancer research.

In Vitro:FCCP (5 μM) results in a concentration-dependent decrease in Aβ and APPsβ production in K695sw cells. FCCP inhibits processing of wild-type APP. FCCP does not alter cellular ATP levels at any of the concentrations measured. The effects of FCCP on APP catabolism are independent of secondary effects on oxidative phosphorylation or the result of reduced cell viability. FCCP (5 μM or 500 nM), baf A1, and NH4Cl induce changes in Tf-Tx and Tf-F cellular fluorescence in K695 cells[1]. FCCP (200 nM) protects and enhances the follicle integrity in cat ovarian tissue during short-term in vitro culture. But FCCP does not appear to exert a beneficial or detrimental effect during ovarian tissue cryopreservation[2].

References:
[1]. Connop BP et al.Novel effects of FCCP [carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone] on amyloid precursor protein processing. J Neurochem. 1999 Apr;72(4):1457-65. [2]. Tanpradit N, et al. Carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP) pre-exposure ensures follicle integrity during in vitro culture of ovarian tissue but not during cryopreservation in the domestic cat model. J Assist Reprod Genet. 2016 Dec;33(12):1621-1631. Epub 2016 Sep 17.

Carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP) pre-exposure ensures follicle integrity during in vitro culture of ovarian tissue but not during cryopreservation in the domestic cat model.[Pubmed:27639998]

J Assist Reprod Genet. 2016 Dec;33(12):1621-1631.

PURPOSE: Temporary and reversible downregulation of metabolism may improve the survival of tissues exposed to non-physiological conditions during transport, in vitro culture, and cryopreservation. The objectives of the study were to (1) optimize the concentration and duration of carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP-a mitochondrial uncoupling agent) exposures for biopsies of domestic cat ovarian tissue and (2) examine the effects of FCCP pre-exposures on follicle integrity after tissue culture and/or cryopreservation. METHODS: Biopsies of cat ovarian tissue were first treated with various concentrations of FCCP (0, 10, 40, or 200 nM) for 10 or 120 min to determine the most suitable pre-exposure conditions. Based on these results, tissues were pre-exposed to 200 nM FCCP for 120 min for the subsequent studies on culture and cryopreservation. In all experiments and for each treatment group, tissue activity and integrity were measured by mitochondrial membrane potential (relative optical density of rhodamine 123 fluorescence), follicular viability (calcein assay), follicular morphology (histology), granulosa cell proliferation (Ki-67 immunostaining), and follicular density. RESULTS: Ovarian tissues incubated with 200 nM FCCP for 120 min led to the lowest mitochondrial activity (1.17 +/- 0.09; P < 0.05) compared to control group (0 nM; 1.30 +/- 0.12) while maintaining a constant percentage of viable follicles (75.3 +/- 7.8 %) similar to the control group (71.8 +/- 11.7 %; P > 0.05). After 2 days of in vitro culture, percentage of viable follicles (78.8 +/- 8.9 %) in similar pre-exposure conditions was higher (P < 0.05) than in the absence of FCCP (61.2 +/- 12.0 %) with percentages of morphologically normal follicles (57.6 +/- 17.3 %) not different from the fresh tissue (70.2 +/- 7.1 %; P > 0.05). Interestingly, percentages of cellular proliferation and follicular density were unaltered by the FCCP exposures. Based on the indicators mentioned above, the FCCP-treated tissue fragments did not have a better follicle integrity after freezing and thawing. CONCLUSIONS: Pre-exposure to 200 nM FCCP during 120 min protects and enhances the follicle integrity in cat ovarian tissue during short-term in vitro culture. However, FCCP does not appear to exert a beneficial or detrimental effect during ovarian tissue cryopreservation.

Novel effects of FCCP [carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone] on amyloid precursor protein processing.[Pubmed:10098849]

J Neurochem. 1999 Apr;72(4):1457-65.

Amyloidogenic processing of the beta-amyloid precursor protein (APP) has been implicated in the pathology of Alzheimer's disease. Because it has been suggested that catabolic processing of the APP holoprotein occurs in acidic intracellular compartments, we studied the effects of the protonophore carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone (FCCP) and the H+-ATPase inhibitor bafilomycin A1 on APP catabolism in human embryonic kidney 293 cells expressing either wild-type or "Swedish" mutant APP. Unlike bafilomycin A1, which inhibits beta-amyloid production in cells expressing mutant but not wild-type APP, FCCP inhibited beta-amyloid production in both cell types. Moreover, the effects of FCCP were independent of alterations in total cellular APP levels or APP maturation, and the concentrations used did not alter either cellular ATP levels or cell viability. Bafilomycin A1, which had no effect on beta-amyloid production in wild-type cells, inhibited endocytosis of fluorescent transferrin, whereas concentrations of FCCP that inhibited beta-amyloid production in these cells had no effect on endosomal function. Thus, in wild-type-expressing cells it appears that the beta-amyloid peptide is not produced in the classically defined endosome. Although bafilomycin A1 decreased beta-amyloid release from cells expressing mutant APP but not wild-type APP, it altered lysosomal function in both cell types, suggesting that in normal cells beta-amyloid is not produced in the lysosome. Although inhibition of beta-amyloid production by bafilomycin A1 in mutant cells may occur via changes in endosomal/lysosomal pH, our data suggest that FCCP inhibits wild-type beta-amyloid production by acting on a bafilomycin A1-insensitive acidic compartment that is distinct from either the endosome or the lysosome.

FCCP is an uncoupler of oxidative phosphorylation in mitochondria. FCCP induces activation of PINK1 leading to Parkin Ser65 phosphorylation.

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