Di Paola Marco, Lorusso Michele
Institute of Biomembranes and Bioenergetics, Consiglio Nazionale delle Ricerche, Bari, Italy.
Biochim Biophys Acta. 2006 Sep-Oct;1757(9-10):1330-7. doi: 10.1016/j.bbabio.2006.03.024. Epub 2006 Apr 7.
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 DeltapH-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 Ca(2+)-loaded mitochondria 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 pro-apoptotic 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, DeltaPsi dependence, reversibility by BSA 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.
长链游离脂肪酸（FFA）根据其实际浓度，对线粒体的能量保存系统产生不同影响。亚微摩尔浓度的花生四烯酸（AA）可挽救bc1复合物质子泵活性依赖于ΔpH的抑制。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增加内膜的质子电导率，起到质子载体的作用。FFA可作为天然解偶联剂，引起轻度解偶联，从而在呼吸静息状态下防止活性氧的产生。当加载Ca(2+)的线粒体暴露于微摩尔浓度的FFA时，内膜通透性增加，导致基质肿胀、外膜破裂和膜间促凋亡蛋白释放。从心脏或肝脏分离的线粒体中，AA诱导的肿胀特征明显不同。在肝脏线粒体中，它呈现出经典通透性转换（PT）的典型特征，而在心脏线粒体中，在环孢菌素A敏感性、ΔΨ依赖性、牛血清白蛋白的可逆性以及激活二价阳离子的特异性方面观察到显著差异。在心脏线粒体中，内膜通透性的AA依赖性增加受腺嘌呤核苷酸和苍术苷等ANT配体的影响。AA显然导致Ca2+介导的ANT从转运体向通道系统的转变。在用二酰胺处理心脏线粒体后，Ca2+/AA诱导的环孢菌素A不敏感通道转变为经典的PT孔。讨论了这些观察结果在假定的PTP的组织特异性成分以及心脏缺血和缺血后过程方面的相关性。
