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How Cardiolipin Peroxidation Alters the Properties of the Inner Mitochondrial Membrane?

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Details

Original languageEnglish
Pages (from-to)15-23
Number of pages9
JournalChemistry and Physics of Lipids
Volume214
Early online date2018
DOIs
Publication statusPublished - Aug 2018
Publication typeA1 Journal article-refereed

Abstract

Cardiolipins have multiple vital functions within biological cell membranes, most notably in the energy metabolism associated with the inner mitochondrial membrane. Considering their essential role, peroxidation of cardiolipins may plausibly have significant effects, as peroxidation is known to alter the functionality of lipid molecules. We used atomistic molecular dynamics simulations to study how peroxidation of cardiolipin affects the properties of the inner mitochondrial membrane. To this end, we explored what happens when varying fractions of fatty acid chains of cardiolipin are replaced by its four different oxidized products in systems modeling the inner mitochondrial membrane. We found that the oxidation of cardiolipin leads to a conformational change both in the backbone/head group and in chain regions of oxidized cardiolipin molecules. The oxidized groups were observed to shift closer to the membrane-water interface region, where they formed hydrogen bonds with several other groups. Additionally, the conformational change turned out to decrease bilayer thickness, and to increase the area per lipid chain, though these changes were minor. The acyl chain conformational order of unoxidized lipids exposed to interactions with oxidized cardiolipins was increased in carbons 3–5 and decreased in carbons 13–17 due to the structural reorganization of the cardiolipin molecules. Overall, the results bring up that the conformation of cardiolipin is altered upon oxidation, suggesting that its oxidation may interfere its interactions with mitochondrial proteins and thereby affect cardiolipin-dependent cellular processes such as electron and proton transport.

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Field of science, Statistics Finland

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