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Papers In Press, published online ahead of print January 31, 2006
J. Lipid Res., doi:10.1194/jlr.D500044-JLR200
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Dept of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110
Corresponding Author: xianlin{at}wustl.edu
Cardiolipin is a prominent component of the mitochondrial inner membrane contributing to the regulation of multiple discrete mitochondrial functions. Herein, we extend shotgun lipidomics to identify and quantitate cardiolipin molecular species directly from lipid extracts of biological samples. Three shotgun lipidomics approaches for analyses of cardiolipin molecular species were developed using either a continuous ion-transmission instrument (i.e., QqQ type) with either low or high mass resolution settings or a high mass resolution hybrid pulsed instrument (i.e., QqTOF type). Three chemical principles were employed for the development of these approaches. These include exploiting the marked enrichment of linoleate in cardiolipin to maximize the signal to noise ratio, the specific neutral loss of ketenes from doubly charged cardiolipin molecular ions to yield doubly charged triacyl monolysocardiolipins, and the doubly charged character of two phosphates in each cardiolipin molecular species. Through these techniques, we identified and quantified the specific molecular species profiles of cardiolipin directly from lipid extracts of mouse heart, liver, and skeletal muscle. The accuracy (~ 5%) and the low end of the linear dynamic range (10 fmol/µl) for quantitation make these approaches useful for studying alterations in cardiolipin metabolism in multiple disease states using either type of mass spectrometer.
Revised on January 30, 2006
Accepted on January 30, 2006
Shotgun lipidomics of cardiolipin molecular species in lipid extracts of biological samples
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