Protein "amyloid-like" networks at the phospholipid membrane formed by 4-hydroxy-2-nonenal-modified mitochondrial creatine kinase.

Q3 Biochemistry, Genetics and Molecular Biology Molecular Membrane Biology Pub Date : 2015-01-01 Epub Date: 2015-04-13 DOI:10.3109/09687688.2015.1023376
Ofelia Maniti, Liberty François-Moutal, Marie-France Lecompte, Christian Vial, Michel Lagarde, Michel Guichardant, Olivier Marcillat, Thierry Granjon
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引用次数: 8

Abstract

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.

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由4-羟基-2-壬烯醛修饰的线粒体肌酸激酶形成的磷脂膜上的蛋白质“淀粉样”网络。
4-羟基-2-壬烯醛(4-HNE)是生物组织在生理和病理条件下形成的活性醛和脂质过氧化产物。它的浓度随着氧化应激而增加,并诱导蛋白质和膜的有害修饰。线粒体和细胞质肌酸激酶的同工型先前已被证明受到4-HNE的影响。在本研究中,我们分析了4-HNE对线粒体肌酸激酶的影响,肌酸激酶是线粒体膜间隙中丰富的蛋白质,在线粒体生理中起关键作用。我们发现这种作用是双重的:4-HNE诱导肌酸激酶活性的逐步丧失以及快速的蛋白质聚集。蛋白质-膜相互作用受到影响,并在仿生膜上形成淀粉样网络。这些原纤维可能在膜和膜间空间扰乱线粒体组织。
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来源期刊
Molecular Membrane Biology
Molecular Membrane Biology 生物-生化与分子生物学
CiteScore
4.80
自引率
0.00%
发文量
0
审稿时长
>12 weeks
期刊介绍: Cessation. Molecular Membrane Biology provides a forum for high quality research that serves to advance knowledge in molecular aspects of biological membrane structure and function. The journal welcomes submissions of original research papers and reviews in the following areas: • Membrane receptors and signalling • Membrane transporters, pores and channels • Synthesis and structure of membrane proteins • Membrane translocation and targeting • Lipid organisation and asymmetry • Model membranes • Membrane trafficking • Cytoskeletal and extracellular membrane interactions • Cell adhesion and intercellular interactions • Molecular dynamics and molecular modelling of membranes. • Antimicrobial peptides.
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