Photoreactive bioorthogonal lipid probes and their applications in mammalian biology.

Lipids are an important class of biological molecules that possess many critical physiological functions, which enable the optimal survival of all organisms, including humans. While the role of lipids in the formation of biological cellular membranes and as a source of energy is fairly well understood, the cellular signalling pathways that lipids modulate in mammals are, in comparison, poorly characterized mechanistically and/or largely unknown. In an effort to dissect these mammalian cellular pathways regulated by signalling lipids and map hitherto unknown protein-lipid interactions, the last two decades have seen tremendous progress in the development of multifunctional lipid probes that, in conjunction with well-established bioorthogonal chemistries and chemoproteomics platforms, has almost exponentially expanded our knowledge in this field. In this review, we focus on the various photoreactive bioorthogonal lipid probes described in the literature, and briefly summarize the different photo-crosslinking groups and bioorthogonal chemistries used by them. Furthermore, we report specific case examples of such photoreactive bioorthogonal lipid probes, and discuss the new biological pathways and insights that have emerged from their use through chemoproteomics in mammalian cells. Finally, we highlight the challenges associated with the use of lipid probes in biological systems, and highlight their importance in the discovery and mechanistic understanding of lipid signalling pathways in the years to come.

The Lysophosphatidylserines-An Emerging Class of Signalling Lysophospholipids.

Lysophospholipids are potent hormone-like signalling biological lipids that regulate many important biological processes in mammals (including humans). Lysophosphatidic acid and sphingosine-1-phosphate represent the best studied examples for this lipid class, and their metabolic enzymes and/or cognate receptors are currently under clinical investigation for treatment of various neurological and autoimmune diseases in humans. Over the past two decades, the lysophsophatidylserines (lyso-PSs) have emerged as yet another biologically important lysophospholipid, and deregulation in its metabolism has been linked to various human pathophysiological conditions. Despite its recent emergence, an exhaustive review summarizing recent advances on lyso-PSs and the biological pathways that this bioactive lysophospholipid regulates has been lacking. To address this, here, we summarize studies that led to the discovery of lyso-PS as a potent signalling biomolecule, and discuss the structure, its detection in biological systems, and the biodistribution of this lysophospholipid in various mammalian systems. Further, we describe in detail the enzymatic pathways that are involved in the biosynthesis and degradation of this lipid and the putative lyso-PS receptors reported in the literature. Finally, we discuss the various biological pathways directly regulated by lyso-PSs in mammals and prospect new questions for this still emerging biomedically important signalling lysophospholipid.