The Role of Reactive Oxygen Species in Mitochondrial Permeability Transition

作者：Aníbal Eugênio Vercesi, Alicia Juliana Kowaltowski, Mercedes T. Grijalba, André R. Meinicke, Roger Frigerio Castilho · 发表于：Bioscience Reports · 年份：1997 · DOI：10.1023/a:1027335217774 · 被引用次数：324 · 研究领域：Mitochondrial Function and Pathology、Adipose Tissue and Metabolism、Metabolomics and Mass Spectrometry Studies

We have provided evidence that mitochondrial membrane permeability transition induced by inorganic phosphate, uncouplers or prooxidants such as t-butyl hydroperoxide and diamide is caused by a Ca(2+)-stimulated production of reactive oxygen species (ROS) by the respiratory chain, at the level of the coenzyme Q. The ROS attack to membrane protein thiols produces cross-linkage reactions, that may open membrane pores upon Ca2+ binding. Studies with submitochondrial particles have demonstrated that the binding of Ca2+ to these particles (possibly to cardiolipin) induces lipid lateral phase separation detected by electron paramagnetic resonance experiments exploying stearic acids spin labels. This condition leads to a disorganization of respiratory chain components, favoring ROS production and consequent protein and lipid oxidation.