mitochondrial pathway for biosynthesis of lipid mediators

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; Kagan, Valerian E.

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mitochondrial pathway for biosynthesis of lipid mediators

Published Date:

Apr 20 2014

Source:

Nat Chem. 6(6):542-552.

[PDF - 2.50 MB]

Details:

Personal Authors:

Tyurina, Yulia Y. ; Poloyac, Samuel M. ; Tyurin, Vladimir A. ; Kapralov, Alexander A. ; Jiang, Jianfei ; ... More ▼

Keywords:

[+]

Pubmed ID:

24848241

Pubmed Central ID:

PMC4201180

Description:

The central role of mitochondria in metabolic pathways and in cell-death mechanisms requires sophisticated signalling systems. Essential in this signalling 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 (CL), is oxidized by the intermembrane-space haemoprotein, cytochrome c. We show that a number of oxygenated CL species undergo phospholipase A2-catalysed hydrolysis and thus generate multiple oxygenated fatty acids, including well-known lipid mediators. This represents a new biosynthetic pathway for lipid mediators. We demonstrate that this pathway, which includes the oxidation of polyunsaturated CLs and accumulation of their hydrolysis products (oxygenated linoleic, arachidonic acids and monolysocardiolipins), is activated in vivo after acute tissue injury.

Document Type:

Journal Article

Collection(s):

CDC Public Access

Funding:

ES020693/ES/NIEHS NIH HHS/United States
ES021068/ES/NIEHS NIH HHS/United States
NS052315/NS/NINDS NIH HHS/United States
NS061817/NS/NINDS NIH HHS/United States
NS076511/NS/NINDS NIH HHS/United States
OH008282/OH/NIOSH CDC HHS/United States
P01 HL114453/HL/NHLBI NIH HHS/United States
P01 HL114453/HL/NHLBI NIH HHS/United States
R01 CA165065/CA/NCI NIH HHS/United States
R01 ES020693/ES/NIEHS NIH HHS/United States
R01 NS061817/NS/NINDS NIH HHS/United States
R01 NS076511/NS/NINDS NIH HHS/United States
R21 ES021068/ES/NIEHS NIH HHS/United States
S10RR023461/RR/NCRR NIH HHS/United States
U19 AI068021/AI/NIAID NIH HHS/United States
U19AIO68021/PHS HHS/United States
UL1 TR000005/TR/NCATS NIH HHS/United States

Supporting Files:

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