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Perhydroxyl Radical (HO2•) as Inducer of the Isoprostane Lipid Peroxidation in Mitochondria

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Abstract

The nonenzymatic isoprostane pathway of lipid peroxidation of polyunsaturated fatty acids results in formation of products, termed isoprostanes, which have very large positional and stereo isomerism, possess various biological activities, produce adducts with proteins, and thus contribute to pathogeneses of the agedependent diseases. However, it was unclear what mechanism drives this type of lipid autoxidation, and why the products have very large isomerism. We propose a mechanism when perhydroxyl radicals (HO2•) react with polyunsaturated fatty acids in the hydrophobic milieu of membranes. In the membrane HO2• initiates a chain of reactions with formation first H2O2, which undergoes homolytic fission producing two •OH radicals, thus very rapidly abstracting three H atoms from a polyunsaturated fatty acid. As a result, the HO2• molecule is converted to two molecules of water, and the molecule of a polyunsaturated fatty acid loses two double bonds, becomes highly unstable and undergoes peroxidation and random intramolecular re-arrangements causing a very large isomerism of the final products. The extremely high reactivity of •HО2 with polyunsaturated fatty acids is the cause of very subtle and slow accumulation of damages in the membrane and membrane associated proteins, even though the concentration of •HО2 relative to superoxide radical may be very low.

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Abbreviations

AA:

arachidonic acid

DHA:

docosahexaenoic acid

FLA2 :

Ca2+-independent phospholipase A2

Е2-IsoК and D2-IsoК:

isoketals with rings Е2 and D2 correspondingly

IsoLG:

isolevuglandins

IsoTxA2 and IsoTxB2 :

isothromboxanes with ring А2 and В2

IMM:

inner mitochondrial membrane

IPPOL:

isoprostane type lipid peroxidation

IsoP:

isoprostane

LP:

lipid peroxidation

OMM:

outer mitochondrial membrane

PG:

prostaglandin

PUFA:

polyunsaturated fatty acid

ROS:

reactive oxygen species

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  1. Institute of Molecular Biology and Biophysics, Siberian Division of the Russian Academy of Sciences, Novosibirsk, 630117, Russia

    A. Panov

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Panov, A. Perhydroxyl Radical (HO2•) as Inducer of the Isoprostane Lipid Peroxidation in Mitochondria. Mol Biol 52, 295–305 (2018). https://doi.org/10.1134/S0026893318020097

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