Mitochondrial uncouplers

Uncouplers of mitochondrial oxidative phosphorylation, including carbonilcyanide p-triflouromethoxyphenylhydrazone (fccp) and carbonilcyanide m-cholorophenylhydrazone (cccp), are widely used in experimental research to investigate the role of mitochondria in cellular function unfortunately, it is very difficult to interpret the results obtained in intact cells using fccp and cccp, as these agents not only inhibit mitochondrial potential, but may also affect membrane potential and cell volume. An uncoupling protein (ucp) is a mitochondrial inner membrane protein that is a regulated proton channel or transporter an uncoupling protein is thus capable of dissipating the proton gradient generated by nadh-powered pumping of protons from the mitochondrial matrix to the mitochondrial intermembrane space.

Mitochondrial proton leak a physiologic process in which oxidative phosphorylation is uncoupled from atp synthesis with energy dissipated as heat protons re-enter the mitochondrial matrix through facilitated diffusion mediated by uncoupling protein-1 (ucp1 thermogenin) without contributing to atp synthesis. We tested two safe mitochondrial uncouplers, nen (niclosamide ethanolamine) and oxyclozanide, on their metabolic effects and anti-cancer activities we used metabolomic nmr to examine the effect of mitochondrial uncoupling on glucose metabolism in colon cancer mc38 cells. That nen and oxyclozanide are mitochondrial uncouplers and determined the efficacious concentrations for uncoupling in colon cancer cells such as mc38 and hct116 cells mitochondrial uncoupling by nen increases pyruvate flux into mitochondria and attenuates ppp.

Mitochondrial uncouplers with an extraordinary dynamic range phing-how lou , birgit s hansen , † preben h olsen , † søren tullin , † michael p murphy , and martin d brand , 1 mrc dunn human nutrition unit, hills road, cambridge cb2 2xy, uk. Small molecule mitochondrial uncouplers transport protons from the mitochondrial inner membrane space into the mitochondrial matrix independent of atp synthase, uncoupling nutrient metabolism from atp generation. Uncoupling proteins (ucps) are mitochondrial transporters present in the inner membrane of mitochondria they are found in all mammals and in plants they belong to the family of anion mitochondrial carriers including adenine nucleotide transporters.

Mitochondrial uncouplers, such as fccp and cccp, have been widely used in investigations into the role of mitochondria in regulation of ca 2+ homeostasis and signalling , , , , fccp and cccp are weak acids that transport protons across the lipid bilayers and depolarise mitochondria by dissipating the proton gradient across the inner membrane. Mitochondrial uncoupling protein 2 an uncoupling protein ( ucp ) is a mitochondrial inner membrane protein that is a regulated proton channel or transporter an uncoupling protein is thus capable of dissipating the proton gradient generated by nadh-powered pumping of protons from the mitochondrial matrix to the mitochondrial intermembrane space. Uncouplers of oxidative phosphorylation in mitochondria inhibit the coupling between the electron transport and phosphorylation reactions and thus inhibit atp synthesis without affecting the respiratory chain and atp synthase (h(+)-atpase.

Mitochondrial uncouplers

Small molecule mitochondrial uncouplers transport protons from the mitochondrial inner membrane space into the mitochondrial matrix independent of atp synthase, uncoupling nutrient metabolism from atp generation the therapeutic potential of mitochondrial uncouplers has been investigated for the treatment of metabolic diseases such as obesity and type 2 diabetes (t2d), ischemia–reperfusion.

mitochondrial uncouplers Weakly acidic uncouplers are considered to produce uncoupling by their protonophoric action in the h(+)-impermeable mitochondrial membrane for exerting these effects, the stability of the respective uncoupler anions in the hydrophobic membrane is very important. mitochondrial uncouplers Weakly acidic uncouplers are considered to produce uncoupling by their protonophoric action in the h(+)-impermeable mitochondrial membrane for exerting these effects, the stability of the respective uncoupler anions in the hydrophobic membrane is very important. mitochondrial uncouplers Weakly acidic uncouplers are considered to produce uncoupling by their protonophoric action in the h(+)-impermeable mitochondrial membrane for exerting these effects, the stability of the respective uncoupler anions in the hydrophobic membrane is very important. mitochondrial uncouplers Weakly acidic uncouplers are considered to produce uncoupling by their protonophoric action in the h(+)-impermeable mitochondrial membrane for exerting these effects, the stability of the respective uncoupler anions in the hydrophobic membrane is very important.
Mitochondrial uncouplers
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2018.