Penetrating Cations Enhance Uncoupling Activity of Anionic Protonophores in Mitochondria

被引：39

作者：

Antonenko, Yuri N. ^{[1
,2
]}

Khailova, Ljudmila S. ^{[1
,2
]}

Knorre, Dmitry A. ^{[1
,2
]}

Markova, Olga V. ^{[1
,2
]}

Rokitskaya, Tatyana I. ^{[1
,2
]}

Ilyasova, Tatyana M. ^{[1
,2
]}

Severina, Inna I. ^{[1
,2
]}

Kotova, Elena A. ^{[1
,2
]}

Karavaeva, Yulia E. ^{[3
]}

Prikhodko, Anastasia S. ^{[3
]}

Severin, Fedor F. ^{[1
,2
]}

Skulachev, Vladimir P. ^{[1
,2
,3
]}

机构：

[1] Moscow MV Lomonosov State Univ, AN Belozersky Inst Physicochem Biol, Moscow, Russia

[2] Moscow MV Lomonosov State Univ, Inst Mitoengn, Moscow, Russia

[3] Moscow MV Lomonosov State Univ, Fac Bioengn & Bioinformat, Moscow, Russia

来源：

PLOS ONE | 2013年 / 8卷 / 04期

基金：

俄罗斯基础研究基金会;

关键词：

BILAYER-LIPID MEMBRANES; OXIDATIVE-PHOSPHORYLATION; TARGETED ANTIOXIDANT; COMPLEX-FORMATION; LIFE-SPAN; CELLS; YEAST; 2,4-DINITROPHENOL; VALINOMYCIN; DERIVATIVES;

D O I：

10.1371/journal.pone.0061902

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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.

引用

页数：13

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