Penetrating cations enhance uncoupling activity of anionic protonophores in mitochondria.
Penetrating cations enhance uncoupling activity of anionic protonophores in mitochondria.
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穿透性阳离子增强了线粒体中阴离子质子团的解耦活性。
DOI：
10.1371/journal.pone.0061902
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Skulachev VP
中科院分区：
文献类型：
--
作者：
Antonenko YN;Khailova LS;Knorre DA;Markova OV;Rokitskaya TI;Ilyasova TM;Severina II;Kotova EA;Karavaeva YE;Prikhodko AS;Severin FF;Skulachev VP
导致线粒体膜电位部分降低的原生生物解偶联剂是治疗应用的有前途的候选药物。在这里，我们发现以膜电位驱动的方式针对线粒体的疏水穿透性阳离子增加了阴离子解偶联剂2，4-二硝基苯酚(DNP)和羰基氰化物-对三氟苯肼(FCCP)的质子转运活性。在分离不同pH值的两个隔室的平面双层类脂膜(BLM)中，十二烷基三苯基膦(C12TPP)的存在增强了DNP介导的H+离子的扩散势。当施加跨膜电位差时，线粒体靶向穿透阳离子显著增加了DNP和间氯苯肼(CCCP)介导的BLM的稳态电流。DNP和FCCP均能抑制含有穿透性阳离子SkQ1的脂质体的羧基荧光素外流。用分光光度法观察到阳离子与CCCP形成络合物。与疏水性较弱的四苯基阳离子(TPP)相比，SkQ1和C12TPP促进了DNP和FCCP对线粒体的解偶联作用。C12TPP和FCCP对降低酵母细胞线粒体膜电位有协同作用。穿透性阳离子对原载体介导的解偶联的刺激作用被认为对低浓度(无毒)原载体的医学应用是有用的。
Protonophorous uncouplers causing a partial decrease in mitochondrial membrane potential are promising candidates for therapeutic applications. Here we showed that hydrophobic penetrating cations specifically targeted to mitochondria in a membrane potential-driven fashion increased proton-translocating activity of the anionic uncouplers 2,4-dinitrophenol (DNP) and carbonylcyanide-p-trifluorophenylhydrazone (FCCP). In planar bilayer lipid membranes (BLM) separating two compartments with different pH values, DNP-mediated diffusion potential of H+ ions was enhanced in the presence of dodecyltriphenylphosphonium cation (C12TPP). The mitochondria-targeted penetrating cations strongly increased DNP- and carbonylcyanide m-chlorophenylhydrazone (CCCP)-mediated steady-state current through BLM when a transmembrane electrical potential difference was applied. Carboxyfluorescein efflux from liposomes initiated by the plastoquinone-containing penetrating cation SkQ1 was inhibited by both DNP and FCCP. Formation of complexes between the cation and CCCP was observed spectophotometrically. In contrast to the less hydrophobic tetraphenylphosphonium cation (TPP), SkQ1 and C12TPP promoted the uncoupling action of DNP and FCCP on isolated mitochondria. C12TPP and FCCP exhibited a synergistic effect decreasing the membrane potential of mitochondria in yeast cells. The stimulating action of penetrating cations on the protonophore-mediated uncoupling is assumed to be useful for medical applications of low (non-toxic) concentrations of protonophores.
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DOI：
10.1111/j.1432-1033.1989.tb14867.x
发表时间：
1989-07-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
ANDREYEV, AY;BONDAREVA, TO;VYGODINA, TV
通讯作者：
VYGODINA, TV
DOI：
10.1046/j.1467-789x.2001.00043.x
发表时间：
2001-11-01
期刊：
Obesity reviews : an official journal of the International Association for the Study of Obesity
影响因子：
--
作者：
Harper, J A;Dickinson, K;Brand, M D
通讯作者：
Brand, M D
DOI：
10.1152/ajpcell.2001.281.3.c825
发表时间：
2001-09-01
影响因子：
5.5
作者：
Jennings, ML;Adame, MF
通讯作者：
Adame, MF
线粒体在信息素酮和胺碘酮诱导的酵母死亡中的作用。
影响因子：
7.8
作者：
Pozniakovsky, Andrei I;Knorre, Dmitry A;Markova, Olga V;Hyman, Anthony A;Skulachev, Vladimir P;Severin, Fedor F
通讯作者：
Severin, Fedor F
影响因子：
4.8
作者：
Barros, MH;Bandy, B;Kowaltowski, AJ
通讯作者：
Kowaltowski, AJ