Palmitic acid opens a novel cyclosporin A-insensitive pore in the inner mitochondrial membrane.
Palmitic acid opens a novel cyclosporin A-insensitive pore in the inner mitochondrial membrane.
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棕榈酸在线粒体内膜上打开一个新的环孢菌素 A 不敏感孔。
DOI：
10.1006/abbi.2000.2194
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
Sokolove,PM
中科院分区：
文献类型：
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作者：
Sultan,A;Sokolove,PM
一种不同的试剂可以诱导线粒体经历通透性转变，这导致线粒体内膜对小(<；1500 Da)溶质非选择性地通透。这种线粒体通透性转变(MPT)的特征是对基质钙离子的严格依赖和对环孢素A(CsA)的敏感性。然而，越来越清楚的是，其他实验条件可以引起线粒体通透性的增加，这与这种经典的MPT截然不同。例如，丁基羟基甲苯(BHT；Sokolove，P.M.和Haley，L.M.(1996)J.BioEnergy.Biomembr28,199-206)和信号肽(Sokolove，P.M.和Kinnally，K.W.(1996)Arch.生物化学。生物群落。336、69-76)促进对CsA不敏感的线粒体通透性增加。有人建议(Gudz，T.，Eriksson，O.，Kushnareva，Y.，Saris，N.E.和Novgorodv，S.A.(1997)Arch.生物化学。生物群落。342,143-156)，BHT可能通过增加磷脂酶A2的活性而打开对CsA不敏感的毛孔，从而产生游离脂肪酸和溶血磷脂的积累。因此，我们研究了饱和游离脂肪酸棕榈酸(PA)对大鼠肝脏线粒体通透性的影响。结果表明：(1)在没有附加触发因素的情况下，PA(20-60μM)可引起浓度依赖的、CsA不敏感的线粒体肿胀。(2)肿胀需要线粒体充能。(3)PA引起的肿胀迅速且无滞后性。(4)Ca~(2+)和Sr~(2+)均支持PA诱导的溶胀，阳离子作用的部位是基质。(5)EGTA和BSA对PA诱导的肿胀有较强的抑制作用。(6)PA不破坏线粒体膜结构，而是开放线粒体膜结构。(7)PA开放的孔道自发闭合。这些结果表明，棕榈酸促进了一种非经典的通透性增加，这与MPT的发生明显不同。
An assortment of agents can induce mitochondria to undergo a permeability transition, which results in the inner mitochondrial membrane becoming nonselectively permeable to small (<1500 Da) solutes. This mitochondrial permeability transition (MPT) is characterized by a strict dependence on matrix Ca2+and sensitivity to cyclosporin A (CsA). However, it is becoming increasingly clear that other experimental conditions can elicit increases in mitochondrial permeability that are distinct from this classic MPT. For example, butylated hydroxytoluene (BHT; Sokolove, P. M., and Haley, L. M. (1996) J. Bioenerg. Biomembr. 28, 199–206) and signal peptides (Sokolove, P. M., and Kinnally, K. W. (1996) Arch. Biochem. Biophys. 336, 69–76) promote increases in mitochondrial permeability that are CsA-insensitive. It has been suggested (Gudz, T., Eriksson, O., Kushnareva, Y., Saris, N.-E., and Novgorodov, S. A. (1997) Arch. Biochem. Biophys. 342, 143–156) that BHT might be opening a CsA-insensitive pore by increasing phospholipase A2activity and thereby producing an accumulation of free fatty acids and lysophospholipids. We have therefore examined the effect of the saturated free fatty acid, palmitic acid (PA), on the permeability of isolated rat liver mitochondria. The following results were obtained: (1) In the absence of additional triggers, PA (20–60 μM) induced concentration-dependent, CsA-insensitive mitochondrial swelling. (2) Swelling required mitochondrial energization. (3) PA-induced swelling was fast and occurred without a lag. (4) Both Ca2+and Sr2+supported PA-induced swelling; the site of cation action was the matrix. (5) EGTA and BSA were potent inhibitors of PA-induced swelling. (6) PA opened a pore rather than disrupting mitochondrial membrane structure. (7) The pore opened by PA closed spontaneously. These results suggest that palmitic acid promotes a nonclassic permeability increase that is clearly distinguishable from the occurrence of the MPT.