4-Hydroxy-2-nonenal (4-HNE) is a reactive aldehyde and a lipid peroxidation product formed in biological tissues under physiological and pathological conditions. Its concentration increases with oxidative stress and induces deleterious modifications of proteins and membranes. Mitochondrial and cytosolic isoforms of creatine kinase were previously shown to be affected by 4-HNE. In the present study, we analyzed the effect of 4-HNE on mitochondrial creatine kinase, an abundant protein from the mitochondrial intermembrane space with a key role in mitochondrial physiology. We show that this effect is double: 4-HNE induces a step-wise loss of creatine kinase activity together with a fast protein aggregation. Protein-membrane interaction is affected and amyloid-like networks formed on the biomimetic membrane. These fibrils may disturb mitochondrial organisation both at the membrane and in the inter membrane space.

4-Hydroxy-2-nonenal（4-HNE）是在生理和病理条件下在生物组织中形成的一种反应性醛和脂质过氧化产物。其浓度随着氧化应激而增加，并诱导蛋白质和膜的有害修饰。先前显示肌酸激酶的线粒体和胞质同工型受4-HNE影响。在本研究中，我们分析了4-HNE对线粒体肌酸激酶的影响，线粒体肌酸激酶是一种来自线粒体膜间空间的丰富蛋白质，在线粒体生理中起关键作用。我们显示这种效果是双重的：4-HNE诱导肌酸激酶活性的逐步损失以及快速的蛋白质聚集。蛋白质-膜的相互作用受到影响，并在仿生膜上形成了淀粉样蛋白样的网络。