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Lou 2007 Biochem J

From Bioblast
Publications in the MiPMap
Lou PH, Hansen BS, Olsen PH, Tullin S, Murphy MP, Brand MD (2007) Mitochondrial uncouplers with an extraordinary dynamic range. Biochem J 407:129-40.

Β» PMID: 17608618 Open Access

Lou PH, Hansen BS, Olsen PH, Tullin S, Murphy MP, Brand MD (2007) Biochem J

Abstract: We have discovered that some weak uncouplers (typified by butylated hydroxytoluene) have a dynamic range of more than 10(6) in vitro: the concentration giving measurable uncoupling is less than one millionth of the concentration causing full uncoupling. They achieve this through a high-affinity interaction with the mitochondrial adenine nucleotide translocase that causes significant but limited uncoupling at extremely low uncoupler concentrations, together with more conventional uncoupling at much higher concentrations. Uncoupling at the translocase is not by a conventional weak acid/anion cycling mechanism since it is also caused by substituted triphenylphosphonium molecules, which are not anionic and cannot protonate. Covalent attachment of the uncoupler to a mitochondrially targeted hydrophobic cation sensitizes it to membrane potential, giving a small additional effect. The wide dynamic range of these uncouplers in isolated mitochondria and intact cells reveals a novel allosteric activation of proton transport through the adenine nucleotide translocase and provides a promising starting point for designing safer uncouplers for obesity therapy. β€’ Keywords: CCCP


Labels: MiParea: Respiration 


Organism: Rat  Tissue;cell: Skeletal muscle, Liver, Islet cell;pancreas;thymus  Preparation: Intact cells, Isolated mitochondria 

Regulation: mt-Membrane potential, Uncoupler  Coupling state: LEAK, ET