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Mitochondrial redox opto-lipidomics reveals mono-oxygenated cardiolipins as pro-apoptotic death signals
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Mao, Gaowei, Qu, Feng, St Croix, Claudette M., Tyurina, Yulia Y., Planas-Iglesias, Joan, Jiang, Jianfei, Huang, Zhentai, Amoscato, Andrew A., Tyurin, Vladimir A., Kapralov, Alexandr A., Cheikhi, Amin, Maguire, John, Klein-Seetharaman, Judith, Bayır, Hülya and Kagan, Valerian E. (2015) Mitochondrial redox opto-lipidomics reveals mono-oxygenated cardiolipins as pro-apoptotic death signals. ACS Chemical Biology, 11 (2). pp. 530-40.
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Official URL: http://pubs.acs.org/doi/abs/10.1021/acschembio.5b0...
Abstract
While opto-genetics has proven to have tremendous value in revealing the functions of the macromolecular machinery in cells, it is not amenable to exploration of small molecules such as phospholipids (PLs). Here, we describe a redox opto-lipidomics approach based on a combination of high affinity light-sensitive ligands to specific PLs in mitochondria with LC-MS based redox lipidomics/bioinformatics analysis for the characterization of pro-apoptotic lipid signals. We identified the formation of mono-oxygenated derivatives of C18:2-containing cardiolipins (CLs) in mitochondria after the exposure of 10-nonylacridine orange bromide (NAO)-loaded cells to light. We ascertained that these signals emerge as an immediate opto-lipidomics response, but they decay long before the commencement of apoptotic cell death. We found that a protonophoric uncoupler caused depolarization of mitochondria and prevented the mitochondrial accumulation of NAO, inhibited the formation of C18:2-CL oxidation product,s and protected cells from death. Redox opto-lipidomics extends the power of opto-biologic protocols to studies of small PL molecules resilient to opto-genetic manipulations.
| Item Type: | Journal Article | ||||
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| Subjects: | Q Science > QD Chemistry Q Science > QH Natural history > QH301 Biology |
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| Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Metabolic and Vascular Health (- until July 2016) | ||||
| Journal or Publication Title: | ACS Chemical Biology | ||||
| Publisher: | American Chemical Society | ||||
| ISSN: | 1554-8929 | ||||
| Official Date: | 23 December 2015 | ||||
| Dates: |
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| Volume: | 11 | ||||
| Number: | 2 | ||||
| Page Range: | pp. 530-40 | ||||
| Status: | Peer Reviewed | ||||
| Publication Status: | Published | ||||
| Access rights to Published version: | Restricted or Subscription Access | ||||
| Funder: | National Institutes of Health (U.S.) (NIH), National Institute for Occupational Safety and and Health (U.S.), National Center for Research Resources (U.S.) (NCRR), Human Frontiers Science Program (HFSP), Barth Syndrome Foundation, Inc. and the Barth Syndrome Foundation of Canada | ||||
| Grant number: | HFSP-RGP0013/2014 |
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