title: Protein "amyloid-like" networks at the phospholipid membrane formed by 4-hydroxy-2-nonenal-modified mitochondrial creatine kinase.
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.
authors: Université de Lyon, Lyon; Université Lyon 1, CNRS, UMR 5246, ICBMS, IMBL , Villeurbanne , France .
authors: Ofelia
authors: O
authors: Maniti
authors: Liberty
authors: L
authors: François-Moutal
authors: Marie-France
authors: MF
authors: Lecompte
authors: Christian
authors: C
authors: Vial
authors: Michel
authors: M
authors: Lagarde
authors: Michel
authors: M
authors: Guichardant
authors: Olivier
authors: O
authors: Marcillat
authors: Thierry
authors: T
authors: Granjon
mesh_terms: D000447:Aldehydes / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D052281:Creatine Kinase, Mitochondrial Form / Q000737:chemistry* / Q000378:metabolism*; D004789:Enzyme Activation; D007425:Intracellular Membranes / Q000378:metabolism*; D015227:Lipid Peroxidation; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism*; D008928:Mitochondria; D010743:Phospholipids / Q000378:metabolism*; D011485:Protein Binding; D055503:Protein Multimerization / Q000187:drug effects; D011994:Recombinant Proteins
chemical_list: D000447:Aldehydes; D008565:Membrane Proteins; D010743:Phospholipids; D011994:Recombinant Proteins; D052281:Creatine Kinase, Mitochondrial Form; C027576:4-hydroxy-2-nonenal
keywords: 4-Hydroxy-2-nonenal; amyloid-like networks; cardiolipin; mitochondrial creatine kinase; protein aggregation