THE ATP-ADP-ANTIPORTER IS INVOLVED IN THE UNCOUPLING EFFECT OF FATTY-ACIDS ON MITOCHONDRIA
THE ATP-ADP-ANTIPORTER IS INVOLVED IN THE UNCOUPLING EFFECT OF FATTY-ACIDS ON MITOCHONDRIA
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DOI：
10.1111/j.1432-1033.1989.tb14867.x
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发表时间：
1989-07-01
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影响因子：
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通讯作者：
VYGODINA, TV
中科院分区：
文献类型：
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作者：
ANDREYEV, AY;BONDAREVA, TO;VYGODINA, TV
ATP/ADP‐反向转运抑制剂和底物ADP抑制低浓度（10-20 μM）棕榈酸盐对骨骼肌和肝脏线粒体的解偶联效应。发现抑制剂和ADP (a)在控制状态下抑制棕榈酸盐刺激的呼吸，(b)增加棕榈酸盐降低的膜电位。效率程度从大到小依次为：羧酸atractyate (CAtr) b> ADP b> bongkrekacid, atractyate。GDP是无效的，Mg b> ADP的影响要小得多，而ATP在比ADP高得多的浓度下是有效的。抑制棕榈酸盐刺激的呼吸的抑制剂浓度与抑制状态3呼吸所需的浓度一致。已发现棕榈酸酯对呼吸的CAtr敏感刺激程度随着棕榈酸酯浓度的增加而降低。三氟甲氧基羰基氰化物苯基氢腙（FCCP）和革兰杀菌素D在任何浓度下对CAtr不敏感，而低浓度的2,4 -二硝基苯酚和十二烷基硫酸盐引起的呼吸刺激被CAtr抑制。棕榈酸酯的上述效果在加入脂肪酸后立即显现。它对EGTA以及磷脂酶（核蛋白酶）和脂质过氧化（离子醇）抑制剂具有抗性。此外，棕榈酸盐在一定条件下促进大鼠肝脏线粒体呼吸控制的自发释放。这种效果需要几分钟，对EGTA、核蛋白酶和离子醇敏感。与快速解偶联一样，ADP抑制这种缓慢效应，而CAtr和atractyate则是刺激而非抑制作用。在人造平面磷脂膜中，棕榈酸酯对膜电导没有明显的提高作用，FCCP对膜电导的提高作用较强，二硝基苯酚对膜电导的提高作用较弱。在细胞色素氧化酶蛋白脂质体中，FCCP、gramicidin和二硝基苯酚（效果较差）降低，而棕榈酸酯增强细胞色素氧化酶生成的膜电位。在这个系统中，莫能菌素代替棕榈酸酯。由此得出结论，ATP/ADP反转运蛋白在一定程度上参与了低浓度棕榈酸盐和二硝基苯酚引起的解偶联作用，而FCCP和gramicidin产生的解偶联作用是由于它们作用于线粒体膜的磷脂部分。讨论了这种效应的可能机理。
The ATP/ADP‐antiporter inhibitors and the substrate ADP suppress the uncoupling effect induced by low (10–20 μM) concentrations of palmitate in mitochondria from skeletal muscle and liver. The inhibitors and ADP are found to (a) inhibit the palmitate‐stimulated respiration in the controlled state and (b) increase the membrane potential lowered by palmitate. The degree of efficiency decreases in the order: carboxyatractylate (CAtr) > ADP > bongkrekic acid, atractylate. GDP is ineffective, Mg > ADP is of much smaller effect, whereas ATP is effective at much higher concentration than is ADP. Inhibitor concentrations, which maximally suppress the palmitate‐stimulated respiration, correspond to those needed for arresting the state 3 respiration. The extent of the CAtr‐sensitive stimulation of respiration by palmitate has been found to decrease with an increase in palmitate concentration. Stimulation of the controlled respiration byp‐trifluoromethoxycarbonylcyanide phenylhydrozone (FCCP) and gramicidin D at any concentrations of these uncouplers is CAtr‐insensitive, whereas that caused by a low concentrations of 2,4‐dinitrophenol and dodecyl sulfate is inhibited by CAtr.The above effect of palmitate develops immediately after addition of the fatty acid. It is resistant to EGTA as well as to inhibitors of phospholipase (nupercain) and of lipid peroxidation (ionol). Moreover, palmitate accelerates spontaneous release of the respiratory control, developing in rat liver mitochondria under certain conditions. This effect takes several minutes, being sensitive to EGTA, nupercain and ionol. Like the fast uncoupling, this slow effect is inhibited by ADP but CAtr and atractylate are stimulatory rather than inhibitory.In artificial planar phospholipid membrane, palmitate does not increase the membrane conductance, FCCP increases it strongly and dinitrophenol only slightly.In cytochrome oxidase proteoliposomes, FCCP, gramicidin and dinitrophenol (less effectively) lower, whereas palmitate enhances the cytochrome‐oxidase‐generated membrane potential. In this system, monensin substitutes for palmitate.It is concluded that the ATP/ADP antiporter is somehow involved in the uncoupling effect caused by low concentrations of palmitate and, partially, of dinitrophenol, whereas uncoupling produced by FCCP and gramicidin is due to their action on the phospholipid part of the mitochondrial membrane. A possible mechanism of this effect is discussed.