Adapted MS/MSALL Shotgun Lipidomics Approach for Analysis of Cardiolipin Molecular Species

Lipids. 2018 Jan;53(1):133-142

Fei Gao, Justice McDaniel, Emily Y. Chen, Hannah E. Rockwell, Cindy Nguyen, Vivek Vishnudas, Matthew D. Lynes, Yu-Hua Tseng, Rangaprasad Sarangarajan, Niven R. Narain, Michael A. Kiebish

Cardiolipin (Ptd₂Gro) is a complex, double-charged phospholipid located in the inner mitochondrial membrane where it plays an essential role in regulating bioenergetics.  Abnormalities in CL content or composition have been associated with mitochondrial dysfunction in a variety of disease states.  Herein, we developed an adapted high-resolution data independent acquisition (DIA) MS/MS^ALL shotgun lipidomic method to enhance the accuracy and reproducibility of Ptd₂Gro molecular species quantitation from biological samples. Utilizing the double charged molecular ions and the isotopic pattern with negative electrospray mode ionization mass spectrometry (ESI-MS) using an adapted MS/MS^ALL approach, we profiled more than 150 individual CL species, including monolysocardiolipin (MLCL). The method described in this study demonstrated high reproducibility, sensitivity, and throughput with a wide dynamic range. This high-resolution MS/MS^ALL shotgun lipidomics approach could be extended to screening aberrations of CL metabolism involved in mitochondrial dysfunction in various pathological conditions and diseases.

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