A mitochondrial pathway for biosynthesis of lipid mediators

Yulia Y. Tyurina; Samuel M. Poloyac; Vladimir A. Tyurin; Alexander A. Kapralov; Jianfei Jiang; Tamil Selvan Anthonymuthu; Valentina I. Kapralova; Anna S. Vikulina; Mi Yeon Jung; Michael W. Epperly; Dariush Mohammadyani; Judith Klein-Seetharaman; Travis C. Jackson; Patrick M. Kochanek; Bruce R. Pitt; Joel S. Greenberger; Yury A. Vladimirov; Hülya Bayir R; Valerian E. Kagan

doi:10.1038/nchem.1924

A mitochondrial pathway for biosynthesis of lipid mediators

Yulia Y. Tyurina, Samuel M. Poloyac, Vladimir A. Tyurin, Alexander A. Kapralov, Jianfei Jiang, Tamil Selvan Anthonymuthu, Valentina I. Kapralova, Anna S. Vikulina, Mi Yeon Jung, Michael W. Epperly, Dariush Mohammadyani, Judith Klein-Seetharaman, Travis C. Jackson, Patrick M. Kochanek, Bruce R. Pitt, Joel S. Greenberger, Yury A. Vladimirov, Hülya Bayir R, Valerian E. Kagan

Research output: Contribution to journal › Article › peer-review

130 Scopus citations

Abstract

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 A 2 -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.

Original language	English (US)
Pages (from-to)	542-552
Number of pages	11
Journal	Nature Chemistry
Volume	6
Issue number	6
DOIs	https://doi.org/10.1038/nchem.1924
State	Published - Jun 2014
Externally published	Yes

ASJC Scopus subject areas

General Chemistry
General Chemical Engineering

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Tyurina, Y. Y., Poloyac, S. M., Tyurin, V. A., Kapralov, A. A., Jiang, J., Anthonymuthu, T. S., Kapralova, V. I., Vikulina, A. S., Jung, M. Y., Epperly, M. W., Mohammadyani, D., Klein-Seetharaman, J., Jackson, T. C., Kochanek, P. M., Pitt, B. R., Greenberger, J. S., Vladimirov, Y. A., Bayir R, H., & Kagan, V. E. (2014). A mitochondrial pathway for biosynthesis of lipid mediators. Nature Chemistry, 6(6), 542-552. https://doi.org/10.1038/nchem.1924

Tyurina, YY, Poloyac, SM, Tyurin, VA, Kapralov, AA, Jiang, J, Anthonymuthu, TS, Kapralova, VI, Vikulina, AS, Jung, MY, Epperly, MW, Mohammadyani, D, Klein-Seetharaman, J, Jackson, TC, Kochanek, PM, Pitt, BR, Greenberger, JS, Vladimirov, YA, Bayir R, H & Kagan, VE 2014, 'A mitochondrial pathway for biosynthesis of lipid mediators', Nature Chemistry, vol. 6, no. 6, pp. 542-552. https://doi.org/10.1038/nchem.1924

@article{87e059bde6494812a4028dcd6d11d092,

title = "A mitochondrial pathway for biosynthesis of lipid mediators",

abstract = "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 A 2 -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.",

author = "Tyurina, {Yulia Y.} and Poloyac, {Samuel M.} and Tyurin, {Vladimir A.} and Kapralov, {Alexander A.} and Jianfei Jiang and Anthonymuthu, {Tamil Selvan} and Kapralova, {Valentina I.} and Vikulina, {Anna S.} and Jung, {Mi Yeon} and Epperly, {Michael W.} and Dariush Mohammadyani and Judith Klein-Seetharaman and Jackson, {Travis C.} and Kochanek, {Patrick M.} and Pitt, {Bruce R.} and Greenberger, {Joel S.} and Vladimirov, {Yury A.} and {Bayir R}, H{\"u}lya and Kagan, {Valerian E.}",

note = "Funding Information: We are thankful to J. L. Millan and S. Narisawa for providing the t-cyt c-specific antibody. We acknowledge support from the National Institutes of Health (ES020693, ES021068, U19AIO68021, PO1 HL114453, NS076511, NS061817, NS052315), the National Institute for Occupational Safety and Health (OH008282), the National Center for Research Resources (S10RR023461), the Human Frontier Science Program (HFSP-RGP0013/2014) and the Fulbright US/Canada Scholar Program.",

year = "2014",

month = jun,

doi = "10.1038/nchem.1924",

language = "English (US)",

volume = "6",

pages = "542--552",

journal = "Nature Chemistry",

issn = "1755-4330",

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T1 - A mitochondrial pathway for biosynthesis of lipid mediators

AU - Tyurina, Yulia Y.

AU - Poloyac, Samuel M.

AU - Tyurin, Vladimir A.

AU - Kapralov, Alexander A.

AU - Jiang, Jianfei

AU - Anthonymuthu, Tamil Selvan

AU - Kapralova, Valentina I.

AU - Vikulina, Anna S.

AU - Jung, Mi Yeon

AU - Epperly, Michael W.

AU - Mohammadyani, Dariush

AU - Klein-Seetharaman, Judith

AU - Jackson, Travis C.

AU - Kochanek, Patrick M.

AU - Pitt, Bruce R.

AU - Greenberger, Joel S.

AU - Vladimirov, Yury A.

AU - Bayir R, Hülya

AU - Kagan, Valerian E.

N1 - Funding Information: We are thankful to J. L. Millan and S. Narisawa for providing the t-cyt c-specific antibody. We acknowledge support from the National Institutes of Health (ES020693, ES021068, U19AIO68021, PO1 HL114453, NS076511, NS061817, NS052315), the National Institute for Occupational Safety and Health (OH008282), the National Center for Research Resources (S10RR023461), the Human Frontier Science Program (HFSP-RGP0013/2014) and the Fulbright US/Canada Scholar Program.

PY - 2014/6

Y1 - 2014/6

N2 - 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 A 2 -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.

AB - 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 A 2 -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.

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JF - Nature Chemistry

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ER -

A mitochondrial pathway for biosynthesis of lipid mediators

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