Completing the cycles; the dynamics of endonuclear lipidomics

Signal transductions via periodic generation and mobilisation of lipid second messengers within the nuclear matrix of eukaryotic cells have focused renewed attention on their precursor phospholipids' location, structure, form and function. The nuclear matrix contains and supports dynamic pools of phosphatidylcholine and phosphatidylinositol which serve as parent molecules of lipid second messengers but also of other phospholipids requiring cyclical replacement as cells proliferate. Applications of new, highly sensitive and specific analytical methodologies based on tandem electrospray ionisation mass spectrometry and the use of stable isotopes have allowed both static and dynamic lipidomic profiling of these endonuclear phospholipid pools. Together with more conventional enzymatic analyses and evaluation of the effect of specific “knock-out” of phospholipid transfer capacity, a number of important principles have been established. Specifically, a compartmental capacity to synthesise and remodel highly saturated phosphatidylcholine exists alongside transport mechanisms that facilitate the nuclear import of phosphatidylinositol and other phospholipids synthesised elsewhere within the cell. Subnuclear fractionation and the use of newly emerging techniques for sensitive lipidomic profiling of polyphosphoinositides, diacylglycerols and phosphatidate molecular species offer the potential for further significant advances in the near future.