mechanism | organic synthesis | chemical biology
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:
Ferroptosis: A Flexible Constellation of Related Biochemical Mechanisms
(a perspective)
Scott J. Dixon* & Derek A. Pratt*
Molecular Cell 2023, 83, 1030-1042
Intramolecular H-Atom Transfers in Alkoxyl Radical Intermediates Underlie the Apparent Oxidation of Lipid Hydroperoxides by Fe(II)
Dmitry D. Saraev, Zijun Wu, Hye-Young Kim, Ned A. Porter & Derek A. Pratt*
ACS Chemical Biology 2023, 18, 2073-2081
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
