Mitochondrial Redox Opto-Lipidomics Reveals Mono-Oxygenated Cardiolipins as Pro-Apoptotic Death Signals

Gaowei Mao, Feng Qu, Claudette M. St. Croix, Yulia Y. Tyurina, Joan Planas-Iglesias, Jianfei Jiang, Zhentai Huang, Andrew A. Amoscato, Vladimir A. Tyurin, Alexandr A. Kapralov, Amin Cheikhi, John Maguire, Judith Klein-Seetharaman, Hülya Baylr, Valerian E. Kagan

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)530-540
Number of pages11
JournalACS Chemical Biology
Volume11
Issue number2
DOIs
StatePublished - Feb 19 2016
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine

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