Novel lipidomic approaches to analyse glycerophospholipids and sphingolipids in complex mixtures using mass spectrometry

Abstract

The development of mass spectrometry (MS) has led to the realisation of a new level of sensitivity, resolution and throughput for simultaneous analysis of multicomponent lipid mixtures, generating a metabolic fingerprint containing quantitative as well as qualitative information on the system investigated. The availability of a wide range of genetic and chemogenetic libraries for various model organisms, including the budding yeast and fruit fly, offers unparalleled opportunities for genome-wide screens to discover and/ or characterise mutants involved in lipid metabolism, transport and turnover, and the revelation of novel lipid functions. A novel MS-based approach for comprehensive profiling of glycerophospholipids and sphingolipids in complex lipid mixtures was developed. The lipidomics approach is further combined with yeast and fly genetics to probe for novel enzymatic activities and modulators of known ones. This study provides evidence of an exquisite specificity of interactions between lipids in living cells that is critical for cellular functions.