Cholesterol Hydroperoxide Generation, Translocation, and Reductive Turnover in Biological Systems

Overview

Journal Cell Biochem Biophys

Specialties Biochemistry
Biophysics
Cell Biology

Date 2017 Apr 24

PMID 28434137

Citations 12

Authors

Albert W Girotti

Witold Korytowski

Affiliations

Soon will be listed here.

Abstract

Cholesterol is like other unsaturated lipids in being susceptible to peroxidative degradation upon exposure to strong oxidants like hydroxyl radical or peroxynitrite generated under conditions of oxidative stress. In the eukaryotic cell plasma membrane, where most of the cellular cholesterol resides, peroxidation leads to membrane structural and functional damage from which pathological states may arise. In low density lipoprotein, cholesterol and phospholipid peroxidation have long been associated with atherogenesis. Among the many intermediates/products of cholesterol oxidation, hydroperoxide species (ChOOHs) have a number of different fates and deserve special attention. These fates include (a) damage-enhancement via iron-catalyzed one-electron reduction, (b) damage containment via two-electron reduction, and (c) inter-membrane, inter-lipoprotein, and membrane-lipoprotein translocation, which allows dissemination of one-electron damage or off-site suppression thereof depending on antioxidant location and capacity. In addition, ChOOHs can serve as reliable and conveniently detected mechanistic reporters of free radical-mediated reactions vs. non-radical (e.g., singlet oxygen)-mediated reactions. Iron-stimulated peroxidation of cholesterol and other lipids underlies a newly discovered form of regulated cell death called ferroptosis. These and other deleterious consequences of radical-mediated lipid peroxidation will be discussed in this review.

Citing Articles

Photosensitized Oxidative Damage from a New Perspective: The Influence of Before-Light and After-Light Reaction Conditions.

Lapoot L, Jabeen S, OConnor R, Korytowski W, Girotti A, Greer A J Org Chem. 2024; 89(18):12873-12885.

PMID: 39231123 PMC: 11421024. DOI: 10.1021/acs.joc.4c01305.

Cholesterol mediated ferroptosis suppression reveals essential roles of Coenzyme Q and squalene.

Sun Q, Liu D, Cui W, Cheng H, Huang L, Zhang R Commun Biol. 2023; 6(1):1108.

PMID: 37914914 PMC: 10620397. DOI: 10.1038/s42003-023-05477-8.

Ferroptosis, autophagy, tumor and immunity.

Xie Y, Zhou Y, Wang J, Du L, Ren Y, Liu F Heliyon. 2023; 9(9):e19799.

PMID: 37810047 PMC: 10559173. DOI: 10.1016/j.heliyon.2023.e19799.

Biological Action of Singlet Molecular Oxygen from the Standpoint of Cell Signaling, Injury and Death.

Fujii J, Soma Y, Matsuda Y Molecules. 2023; 28(10).

PMID: 37241826 PMC: 10223444. DOI: 10.3390/molecules28104085.

Dose-Response Effects of 7-Dehydrocholesterol Reductase Inhibitors on Sterol Profiles and Vesicular Stomatitis Virus Replication.

Korade Z, Tallman K, Kim H, Balog M, Genaro-Mattos T, Pattnaik A ACS Pharmacol Transl Sci. 2022; 5(11):1086-1096.

PMID: 36407960 PMC: 9667548. DOI: 10.1021/acsptsci.2c00051.

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