Special issue: Regulation of lipid metabolism in yeast.

The complexity and dynamic nature of the “lipidome” of eukaryotic cells are increasingly apparent. Taking into account the diversity within many lipid classes created by variability in such factors as acyl chain substitutions, degree of desaturation, hydroxylation, and phosphorylation, the number of molecular species in eukaryotic cells exceeds one thousand. Such estimates of the diversity of the lipidome do not even account for the various water-soluble turnover products of lipid metabolism, many of which are vital signaling molecules themselves. Furthermore, specialized lipids serve to modify proteins and to target and anchor them to specific membranes. Understanding of the complex cellular roles played by lipids, as well as their precursors and turnover products, in signaling, membrane trafficking, and transcriptional networks continues to expand. The regulation of synthesis, turnover, and trafficking of lipids of all classes is extraordinarily complex, but major progress has been made recently in deciphering the mechanisms underlying these processes in a number of eukaryotic cell systems. In the context of these advances, the yeast model system has an important role to play. The powerful tools of yeast molecular and classical genetics enable the cellular functions of gene products to be probed individually and in combination with an ease not possible in any other eukaryotic organism. The advantages of using these genetic approaches in yeast have already been amply demonstrated in the dissection of complex cellular functions such as cell division and membrane trafficking. The time is now ripe to fully exploit the advantages of the yeast system to explore the complex cellular roles of the constituents of the lipidome. As discussed in a number of the papers in this special issue, yeast cells synthesize the same general classes of lipids found in other eukaryotes via pathways largely homologous to those in mammalian cells. In a number of cases, identification of yeast genes involved in various aspects of lipid metabolism has enabled identification of their mammalian counterparts. It is true that the lipids found in yeast exhibit some specific differences from the lipids found in mammalian cells. For example, yeast synthesizes ergosterol as its major sterol instead of cholesterol, and produces sphingolipids containing inositol rather than choline. Furthermore, yeast cells synthesize phosphatidylserine by a mechanism different from that employed by