Penetrating cation/fatty acid anion pair as a mitochondria-targeted protonophore

被引：171

作者：

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

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

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

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

Cherepanov, Dmitry A. ^{[3
]}

Mokhova, Elena N. ^{[1
,2
]}

Vyssokikh, Mikhail Yu. ^{[1
,2
]}

Pustovidko, Antonina V. ^{[1
,2
]}

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

Yaguzhinsky, Lev S. ^{[1
,2
]}

Korshunova, Galina A. ^{[1
,2
]}

Sumbatyan, Nataliya V. ^{[1
,2
]}

Skulachev, Maxim V. ^{[1
,2
]}

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

机构：

[1] Moscow MV Lomonosov State Univ, Belozersky Inst Phys Chem Biol, Moscow 119991, Russia

[2] Moscow MV Lomonosov State Univ, Inst Mitoengn, Moscow 119991, Russia

[3] Russian Acad Sci, Frumkin Inst Phys Chem & Electrochem, Moscow 119991, Russia

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2010年 / 107卷 / 02期

关键词：

mild uncoupling; membrane; Mitochondria-targeted uncoupler; penetrating ion; antioxidant; PLASTOQUINONE DERIVATIVES; INTERRUPT EXECUTION; OXIDATIVE-PHOSPHORYLATION; REACTIVE OXYGEN; FATTY-ACIDS; UNCOUPLING ACTIVITY; RESPIRATORY-CHAIN; LIFE-SPAN; TOOLS; SKQ1;

D O I：

10.1073/pnas.0910216107

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：

07 ; 0710 ; 09 ;

摘要：

A unique phenomenon of mitochondria-targeted protonophores is described. It consists in a transmembrane H+-conducting fatty acid cycling mediated by penetrating cations such as 10-(6'-plastoquinonyl) decyltriphenylphosphonium (SkQ1) or dodecyltriphenylphosphonium (C12TPP). The phenomenon has been modeled by molecular dynamics and directly proved by experiments on bilayer planar phospholipid membrane, liposomes, isolated mitochondria, and yeast cells. In bilayer planar phospholipid membrane, the concerted action of penetrating cations and fatty acids is found to result in conversion of a pH gradient (Delta pH) to a membrane potential (Delta psi) of the Nernstian value (about 60 mV Delta psi at Delta pH = 1). A hydrophobic cation with localized charge (cetyltrimethylammonium) failed to substitute for hydrophobic cations with delocalized charge. In isolated mitochondria, SkQ1 and C12TPP, but not cetyltrimethylammonium, potentiated fatty acid-induced(i) uncoupling of respiration and phosphorylation, and(ii) inhibition of H2O2 formation. In intact yeast cells, C12TPP stimulated respiration regardless of the extracellular pH value, whereas a nontargeted protonophorous uncoupler (trifluoromethoxycarbonylcyanide phenylhydrazone) stimulated respiration at pH 5 but not at pH 3. Hydrophobic penetrating cations might be promising to treat obesity, senescence, and some kinds of cancer that require mitochondrial hyperpolarization.

引用

页码：663 / 668

页数：6

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