Interaction of free fatty acids with mitochondria: Coupling, uncoupling and penneability transition
Interaction of free fatty acids with mitochondria: Coupling, uncoupling and penneability transition
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DOI：
10.1016/j.bbabio.2006.03.024
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发表时间：
2006-09-01
影响因子：
4.3
通讯作者：
Lorusso, Michele
中科院分区：
文献类型：
--
作者：
Di Paola, Marco;Lorusso, Michele
长链游离脂肪酸（FFA）根据其实际浓度的不同，对线粒体的能量守恒系统产生不同的影响。亚微摩尔浓度的花生四烯酸 (AA) 可挽救 bc1 复合物质子泵送活性的 Delta pH 依赖性抑制。这种效应似乎是由于 AA 与泵的质子输入口直接相互作用所致。在微摩尔浓度下，FFA 会增加充当质子载体的内膜的质子电导。 FFA 可以充当天然解偶联剂，引起温和的解偶联，从而防止呼吸静息状态下活性氧的产生。当负载 Ca2+ 的线粒体暴露于微摩尔浓度的 FFA 时，内膜的通透性增加，导致基质膨胀、外膜破裂并释放膜间促凋亡蛋白。 AA 诱导的肿胀特征在从心脏或肝脏分离的线粒体中表现出明显不同。虽然后者呈现出经典通透性转变 (PT) 的典型特征，但在心脏线粒体中，在 CsA 敏感性、Delta psi 依赖性、BSA 的可逆性和激活二价阳离子的特异性方面观察到显着差异。在心脏线粒体中，AA 依赖性的内膜通透性增加受到 ANT 配体（如腺嘌呤核苷酸和白术苷）的影响。 AA 显然会导致 Ca2+ 介导的 ANT 从转运蛋白转化为通道系统。对心脏线粒体进行二酰胺处理后，Ca2+/AA 诱导的 CsA 不敏感通道转化为经典的 PT 孔。讨论了这些观察结果在假定 PTP 的组织特异性成分和心脏缺血和缺血后过程方面的相关性。 (c) 2006 Elsevier B.V. 保留所有权利。
Long chain free fatty acids (FFA) exert, according to their actual concentration, different effects on the energy conserving system of mitochondria. Sub-micromolar concentrations of arachidonic acid (AA) rescue Delta pH-dependent depression of the proton pumping activity of the bc1 complex. This effect appears to be due to a direct interaction of AA with the proton-input mouth of the pump. At micromolar concentrations FFA increase the proton conductance of the inner membrane acting as protonophores. FFA can act as natural uncouplers, causing a mild uncoupling, which prevents reactive oxygen species production in the respiratory resting state. When Ca2+-loaded mitocbondria are exposed to micromolar concentrations of FFA, the permeability of the inner membrane increases, resulting in matrix swelling, rupture of the outer membrane and release of intermembrane proapoptotic proteins. The characteristics of AA-induced swelling appear markedly different in mitochondria isolated from heart or liver. While in the latter it presents the canonical features of the classical permeability transition (PT), in heart mitochondria substantial differences are observed concerning CsA sensitivity, Delta psi dependence, reversibility by B SA and specificity for the activating divalent cation. In heart mitochondria, the AA-dependent increase of the inner membrane permeability is affected by ANT ligands such as adenine nucleotides and atractyloside. AA apparently causes a Ca2+-mediated conversion of ANT from a translocator to a channel system. Upon diamide treatment of heart mitochondria, the Ca2+/AA-induced CsA insensitive channel is converted into the classical PT pore. The relevance of these observations in terms of tissue-specific components of the putative PTP and heart ischemic and post-ischemic process is discussed. (c) 2006 Elsevier B.V. All rights reserved.