Journal article
Ferritin couples iron and fatty acid metabolism
The FASEB journal, v 26(6), pp 2394-2400
Jun 2012
PMID: 22362897
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
A physiological relationship between iron, oxidative injury, and fatty acid metabolism exists, but transduction mechanisms are unclear. We propose that the iron storage protein ferritin contains fatty acid binding sites whose occupancy modulates iron uptake and release. Using isothermal microcalorimetry, we found that arachidonic acid binds ferritin specifically and with 60 μM affinity. Arachidonate binding by ferritin enhanced iron mineralization, decreased iron release, and protected the fatty acid from oxidation. Cocrystals of arachidonic acid and horse spleen apoferritin diffracted to 2.18 Å and revealed specific binding to the 2-fold intersubunit pocket. This pocket shields most of the fatty acid and its double bonds from solvent but allows the arachidonate tail to project well into the ferrihydrite mineralization site on the ferritin L-subunit, a structural feature that we implicate in the effects on mineralization by demonstrating that the much shorter saturated fatty acid, caprylate, has no significant effects on mineralization. These combined effects of arachidonate binding by ferritin are expected to lower both intracellular free iron and free arachidonate, thereby providing a previously unrecognized mechanism for limiting lipid peroxidation, free radical damage, and proinflammatory cascades during times of cellular stress.—Bu, W., Liu, R., Cheung-Lau, J. C., Dmochowski, I. J., Loll, P. J., Eckenhoff, R. G. Ferritin couples iron and fatty acid metabolism.
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Details
- Title
- Ferritin couples iron and fatty acid metabolism
- Creators
- Weiming Bu - Department of Anesthesiology and Critical Care, Perelman School of Medicine, andRenyu Liu - Department of Anesthesiology and Critical Care, Perelman School of Medicine, andJasmina C Cheung-Lau - Department of Chemistry, School of Arts and Sciences, University of Pennsylvania., Philadelphia, Pennsylvania, USA; andIvan J Dmochowski - Department of Chemistry, School of Arts and Sciences, University of Pennsylvania., Philadelphia, Pennsylvania, USA; andPatrick J Loll - Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, Pennsylvania, USARoderic G Eckenhoff - Department of Anesthesiology and Critical Care, Perelman School of Medicine, and
- Publication Details
- The FASEB journal, v 26(6), pp 2394-2400
- Publisher
- Federation of American Societies for Experimental Biology; Bethesda, MD, USA
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology
- Web of Science ID
- WOS:000305017200017
- Scopus ID
- 2-s2.0-84861788364
- Other Identifier
- 991014877876004721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Biology
- Cell Biology