A personal journey with bioactive lipids

Abstract

The concept of lipids acting as signaling and regulatory molecules is now taken for granted. However 3–4 decades ago, this was a rather unthinkable proposition even though the “writing was on the wall” since at least the 1950s. Here, I summarize briefly key historical landmarks in the evolution of the field of bioactive lipids and then describe studies from my group over 3 decades, focusing on the contemporaneous development of understanding of bioactive sphingolipids.Lipid‐based signaling modules. A stimulus (e.g., in the form of a receptor ligand) provides the Input whereas a regulated enzyme is the transducer of the input. There are at least 30 distinct enzymes (products of distinct genes) involved in regulating the levels of the key bioactive sphingolipids. The lipid product, through interaction with distinct targets, provides the Output in this simplest formulation of lipid‐mediated signaling. The diversity of bioactive sphingolipids, especially with the 2 dozen enzymes involved in ceramide generation and the more than 100 distinct ceramides, provides for unprecedented specialization and richness of sphingolipid‐mediated cell regulation.