TY - JOUR
T1 - Mitochondrial Redox Opto-Lipidomics Reveals Mono-Oxygenated Cardiolipins as Pro-Apoptotic Death Signals
AU - Mao, Gaowei
AU - Qu, Feng
AU - St. Croix, Claudette M.
AU - Tyurina, Yulia Y.
AU - Planas-Iglesias, Joan
AU - Jiang, Jianfei
AU - Huang, Zhentai
AU - Amoscato, Andrew A.
AU - Tyurin, Vladimir A.
AU - Kapralov, Alexandr A.
AU - Cheikhi, Amin
AU - Maguire, John
AU - Klein-Seetharaman, Judith
AU - Baylr, Hülya
AU - Kagan, Valerian E.
N1 - Funding Information:
This work was supported by the National Institutes of Health (EB17268, ES020693, U19AIO68021, HL114453, NS076511, NS061817, NS052315, CA 165065), the National Institute for Occupational Safety and Health (OH008282), the National Center for Research Resources (S10RR023461), Human Frontier Science Program (HFSP-RGP0013/2014), and the Barth Syndrome Foundation, Inc. and the Barth Syndrome Foundation of Canada. We are grateful to M. Bruchez (Carnegie Mellon University) for providing dyes and reagents associated with the FAP technology, and M. Larsson of the Center for Biologic Imaging at the University.
Publisher Copyright:
© 2015 American Chemical Society.
PY - 2016/2/19
Y1 - 2016/2/19
N2 - 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.
AB - 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.
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U2 - 10.1021/acschembio.5b00737
DO - 10.1021/acschembio.5b00737
M3 - Article
C2 - 26697918
AN - SCOPUS:84959374249
SN - 1554-8929
VL - 11
SP - 530
EP - 540
JO - ACS Chemical Biology
JF - ACS Chemical Biology
IS - 2
ER -