Masini A, Ceccarelli D, Trenti T, Corongiu F P, Muscatello U
Istituto di Patologia Generale, Università di Modena, Italy.
Biochim Biophys Acta. 1989 Nov 20;1014(2):133-40. doi: 10.1016/0167-4889(89)90025-6.
The functional state of isolated mitochondria and specifically the integrity of the inner membrane, were investigated in the liver of rats made siderotic by dietary supplementation with carbonyl iron. The concentration of iron in the hepatic tissue increased progressively up to nearly 40 days and reached a steady-state level. When the iron content reached a threshold value (higher than 90 nmol/mg protein) the occurrence of in vivo lipid peroxidation in the mitochondrial membrane was detected. This process did not result in gross alterations in the mitochondrial membrane, as indicated by electron microscopy, phosphorylative capability and membrane potential measurements. On the contrary, the induction of lipoperoxidative reaction appeared to be associated with the activation of Ca2+ release from mitochondria. This was shown to occur as a consequence of rather subtle modifications in the inner membrane structure via a specific efflux route, which appeared to be linked to the oxidation level of mitochondrial pyridine nucleotides. The induction of this Ca2+ release from iron-treated mitochondria resulted in enhancement of Ca2+ cycling, a process which dissipates energy to reaccumulate into mitochondria the released Ca2+. The perturbation in mitochondrial Ca2+ homeostasis reported here may be a factor in the onset of cell damage in this experimental model of hepatic iron overload.
通过向大鼠饮食中补充羰基铁使其患高铁症，在此情况下研究了分离线粒体的功能状态，特别是内膜的完整性。肝组织中铁的浓度逐渐升高，直至近40天时达到稳态水平。当铁含量达到阈值（高于90 nmol/mg蛋白质）时，检测到线粒体膜中发生体内脂质过氧化。如电子显微镜、磷酸化能力和膜电位测量所示，该过程并未导致线粒体膜出现明显改变。相反，脂质过氧化反应的诱导似乎与线粒体Ca2+释放的激活有关。这表明它是通过特定的外排途径对内膜结构进行相当细微的修饰而产生的结果，这一途径似乎与线粒体吡啶核苷酸的氧化水平有关。铁处理的线粒体中这种Ca2+释放的诱导导致Ca2+循环增强，这一过程会消耗能量以将释放的Ca2+重新积累到线粒体中。此处报道的线粒体Ca2+稳态的扰动可能是该肝铁过载实验模型中细胞损伤发生的一个因素。
