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Lipid Peroxidation and Ferroptosis

The unsaturated carbon-carbon bonds of fatty acids and cholesterol derivatives which abound the cell membrane (and the membranes of the organelles found within) make them vulnerable to autoxidation. This process, also called lipid peroxidation, has long been implicated in degenerative disease, but only recently has this been linked via a specific type of cell death called ferroptosis. We study the molecular mechanisms of lipid peroxidation in order to better understand the origin of the products that are observed from the various classes of lipid (i.e. monounsaturated and polyunsaturated fatty acids, cholesterol and its derivatives and plasmalogens). Moreover, we study how these products/processes contribute to ferroptosis and use this information in order to design, synthesize and develop better tools to study this type of cell death (e.g. imaging agents, biomarkers).   

Check out some representative work from our lab:

On the Products of Cholesterol Autoxidation in Phospholipid Bilayers and the Formation of Secosterols Derived Therefrom 

Emily L. Schaefer, Nadia Zopyrus, Zosia A. M. Zielinski & Derek A. Pratt*

Angewandte Chemie International Edition 2020, 59, 2089-2094

The Chemical Basis of Ferroptosis

(a perspective)

Marcus Conrad* & Derek A. Pratt*

Nature Chemical Biology 2019, 15, 1137-1147.

 

H-Atom Abstraction vs. Addition: Accounting for the Diverse Product Distribution in the Autoxidation of Cholesterol & its Esters

Zosia A. M. Zielinski & Derek A. Pratt*

Journal of the American Chemical Society 2019, 141, 3037-3051

 

Resolving the Role of Lipoxygenases in the Initiation and Execution of Ferroptosis

Ron Shah, Mikhail S. Shchepinov & Derek A. Pratt*

ACS Central Science 2018, 4, 387-396

Lipid Peroxidation: Kinetics, Mechanisms and Products

(a synopsis)

Zosia A. M. Zielinski & Derek A. Pratt* 

Journal of Organic Chemistry 2017, 82, 2817-2825

Cholesterol Autoxidation Revisited: Debunking the Dogma Associated with the Most Vilified of Lipids

Zosia Zielinski & Derek A. Pratt* 

Journal of the American Chemical Society 2016138, 6932-6935

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