Abstract
The primacy of lipids as essential components of cellular membranes is conserved across taxonomic domains. In addition to this crucial role as a semi-permeable barrier, lipids are also increasingly recognized as important signaling molecules with diverse functional mechanisms ranging from cell surface receptor binding to the intracellular regulation of enzymatic cascades. In this review, we focus on ether lipids, an ancient family of lipids having ether-linked structures that chemically differ from their more prevalent acyl relatives. In particular, we examine ether lipid biosynthesis in the peroxisome of mammalian cells, the roles of selected glycerolipids and glycerophospholipids in signal transduction in both prokaryotes and eukaryotes, and finally, the potential therapeutic contributions of synthetic ether lipids to the treatment of cancer.
Highlights
Much like many other types of organic molecules, lipids are essential for life—even ancient life
Some of these signaling lipids such as diacylglycerol (DAG) and lysophosphatidic acid (LPA) are endogenously produced by the action of many isoforms of phospholipase enzymes, while others are derived from the oxidation of essential, polyunsaturated fatty acids (PUFA), including arachidonic acid, ω-3 or ω-6 fatty acids
PUFA can be further oxidized into oxylipins, a large group of signaling lipids that regulate an expansive array of metazoan vascular responses such as platelet aggregation and clot resolution, innate immunity and inflammation [5,6,7]
Summary
Much like many other types of organic molecules, lipids are essential for life—even ancient life. Since the coining of the term “prostaglandin” by the Swedish scientist Ulf von Euler in the 1930s [4], a multitude of bioactive lipid mediators have been discovered that can act as signaling molecules making this aspect of lipid function no longer considered foreign, but increasingly recognized as a significant part of cellular behavior Some of these signaling lipids such as diacylglycerol (DAG) and lysophosphatidic acid (LPA) are endogenously produced by the action of many isoforms of phospholipase enzymes, while others are derived from the oxidation of essential, polyunsaturated fatty acids (PUFA), including arachidonic acid, ω-3 or ω-6 fatty acids. Due to the presence of other timely and comprehensive reviews [12,13,14], we will focus mainly on the signaling properties of naturally derived glycerolipids and phosphoglycerolipids, their synthetic mimetics designed to interfere with key signaling networks in human disease and briefly, their abundant membrane counterparts, the plasmalogens, about which much has been written already
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