Abstract
Lipidomics is a rapidly expanding research field in which multiple techniques are utilized to quantitate the hundreds of chemically distinct lipids in cells and determine the molecular mechanisms through which they facilitate cellular function. Recent developments in electrospray ionization mass spectrometry (ESI/MS) have made possible, for the first time, the precise identification and quantification of alterations in a cell's lipidome after cellular perturbations. This review provides an overview of the essential role of ESI/MS in lipidomics, presents a broad strategy applicable for the generation of lipidomes directly from cellular extracts of biological samples by ESI/MS, and summarizes salient examples of strategies utilized to conquer the lipidome in physiologic signaling as well as pathophysiologically relevant disease states. Because of its unparalleled sensitivity, specificity, and efficiency, ESI/MS has provided a critical bridge to generate highly accurate data that fingerprint cellular lipidomes to facilitate insight into the functional role of subcellular membrane compartments and microdomains in mammalian cells. We believe that ESI/MS-facilitated lipidomics has now opened a critical door that will greatly increase our understanding of human disease.
Highlights
PRINCIPLES OF electrospray ionization (ESI)ESI is an ionization technique used for the mass spectrometric analysis of polar compounds that was initially developed by Fenn and colleagues [15]
Lipidomics is a rapidly expanding research field in which multiple techniques are utilized to quantitate the hundreds of chemically distinct lipids in cells and determine the molecular mechanisms through which they facilitate cellular function
These results suggest that alterations in specific lipidomes may play an important role in the pathogenesis of Alzheimer’s disease (AD) and may be linked with early events in the pathological process of AD, including neurodegeneration, synapse loss, and synaptic dysfunction in AD
Summary
ESI is an ionization technique used for the mass spectrometric analysis of polar compounds that was initially developed by Fenn and colleagues [15]. A typical negative-ion ESI/MS mass spectrum of a mouse myocardial lipid extract (Fig. 3A) demonstrates multiple abundant anionic phospholipid molecular species that have been identified by tandem MS [25, 36]. A typical positive-ion ESI/MS mass spectrum of a mouse myocardial lipid extract (the identical extract used for the acquisition of Fig. 3B) demonstrates multiple abundant choline-containing phospholipid molecular species (Fig. 3C). Negative-ion ESI tandem MS with NL scanning of mass 240.2 units of a mouse myocardial lipid extract in the presence of a small amount of LiOH Deconvolution of overlapping and isobaric peaks in the positive-ion ESI mass spectra of lipid extracts by two-dimensional fatty acyl group analyses is accomplished by iterative processing resulting in a detailed molecular species fingerprint of individual TAG molecular species directly from chloroform extracts of biological samples. Other soft ionization techniques of MS, such as atmospheric pressure chemical ionization, which has recently been reviewed [43], may be employed to analyze these nonpolar lipids
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