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A mitochondrial pathway for biosynthesis of lipid mediators
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Tyurina, Yulia Y., Poloyac, Samuel M., Tyurin, Vladimir A., Kapralov, Alexander A., Jiang, Jianfei, Anthonymuthu, Tamil Selvan, Kapralova, Valentina I., Vikulina, Anna S., Jung, Mi-Yeon, Epperly, Michael W., Mohammadyani, Dariush, Klein-Seetharaman, Judith, Jackson, Travis C., Kochanek, Patrick M., Pitt, Bruce R., Greenberger, Joel S., Vladimirov, Yury A., Bayır, Hülya and Kagan, Valerian E. (2014) A mitochondrial pathway for biosynthesis of lipid mediators. Nature Chemistry, 6 (6). pp. 542-552. doi:10.1038/nchem.1924 ISSN 1755-4330.
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Official URL: http://dx.doi.org/10.1038/nchem.1924
Abstract
The central role of mitochondria in metabolic pathways and in cell death mechanisms requires sophisticated signaling systems. Essential in this signaling process is an array of lipid mediators derived from polyunsaturated fatty acids. However, the molecular machinery for the production of oxygenated polyunsaturated fatty acids is localized in the cytosol and their biosynthesis has not been identified in mitochondria. Here we report that a range of diversified polyunsaturated molecular species derived from a mitochondria-specific phospholipid, cardiolipin, are oxidized by the intermembrane space hemoprotein, cytochrome c. We show that an assortment of oxygenated cardiolipin species undergoes phospholipase A2-catalyzed hydrolysis thus generating multiple oxygenated fatty acids, including well known lipid mediators. This represents a new biosynthetic pathway for lipid mediators. We demonstrate that this pathway including oxidation of polyunsaturated cardiolipins and accumulation of their hydrolysis products – oxygenated linoleic, arachidonic acids and monolyso-cardiolipins – is activated in vivo after acute tissue injury.
Item Type: | Journal Article | ||||||||
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Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Metabolic and Vascular Health (- until July 2016) Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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Journal or Publication Title: | Nature Chemistry | ||||||||
Publisher: | Nature Publishing Group | ||||||||
ISSN: | 1755-4330 | ||||||||
Official Date: | 20 April 2014 | ||||||||
Dates: |
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Volume: | 6 | ||||||||
Number: | 6 | ||||||||
Page Range: | pp. 542-552 | ||||||||
DOI: | 10.1038/nchem.1924 | ||||||||
Status: | Peer Reviewed | ||||||||
Publication Status: | Published | ||||||||
Access rights to Published version: | Restricted or Subscription Access |
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