Mitochondrial Redox Opto-Lipidomics Reveals Mono-Oxygenated Cardiolipins as Pro-Apoptotic Death Signals.
Mitochondrial Redox Opto-Lipidomics Reveals Mono-Oxygenated Cardiolipins as Pro-Apoptotic Death Signals.
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DOI：
10.1021/acschembio.5b00737
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发表时间：
2016-02-19
影响因子：
4
通讯作者：
Kagan VE
中科院分区：
文献类型：
--
作者：
Mao G;Qu F;St Croix CM;Tyurina YY;Planas-Iglesias J;Jiang J;Huang Z;Amoscato AA;Tyurin VA;Kapralov AA;Cheikhi A;Maguire J;Klein-Seetharaman J;Bayır H;Kagan VE
虽然光遗传学已被证明在揭示细胞大分子机制的功能方面具有巨大的价值，但它并不适用于磷脂（PLs）等小分子的探索。在这里，我们描述了一种氧化还原光脂组学方法，该方法基于将线粒体中特定PLs的高亲和力光敏配体与基于LC-MS的氧化还原脂组学/生物信息学分析相结合，以表征促凋亡脂质信号。我们发现，在10-壬基吖啶橙溴（NAO）负载细胞暴露于光后，线粒体中含有c18:2的单氧衍生物（CLs）形成。我们确定这些信号作为一个直接的光脂组反应出现，但它们在凋亡细胞死亡开始之前就衰减了。我们发现一个原滋养解偶联剂引起线粒体去极化，阻止线粒体NAO的积累，抑制C18:2-CL氧化产物的形成，保护细胞免于死亡。氧化还原光脂组学将光生物学协议的力量扩展到对光遗传操作具有弹性的小PL分子的研究。
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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影响因子：
64.5
作者：
Dixon SJ;Lemberg KM;Lamprecht MR;Skouta R;Zaitsev EM;Gleason CE;Patel DN;Bauer AJ;Cantley AM;Yang WS;Morrison B 3rd;Stockwell BR
通讯作者：
Stockwell BR
影响因子：
4.2
作者：
Ji, Jing;Tyurina, Yulia Y.;Bayir, Huelya
通讯作者：
Bayir, Huelya
影响因子：
3.4
作者：
deKroon, AIPM;Dolis, D;deKruijff, B
通讯作者：
deKruijff, B
影响因子：
3.5
作者：
Giraldo, AMV;Castello, PR;Rossi, JPFC
通讯作者：
Rossi, JPFC
影响因子：
21.3
作者：
Friedmann Angeli JP;Schneider M;Proneth B;Tyurina YY;Tyurin VA;Hammond VJ;Herbach N;Aichler M;Walch A;Eggenhofer E;Basavarajappa D;Rådmark O;Kobayashi S;Seibt T;Beck H;Neff F;Esposito I;Wanke R;Förster H;Yefremova O;Heinrichmeyer M;Bornkamm GW;Geissler EK;Thomas SB;Stockwell BR;O'Donnell VB;Kagan VE;Schick JA;Conrad M
通讯作者：
Conrad M