How has the evolution of our understanding of the compartmentalization of sphingolipid biosynthesis over the past 30 years altered our view of the evolution of the pathway?

Abstract

Sphingolipids are unique among cellular lipids inasmuch as their biosynthesis is compartmentalized between the endoplasmic reticulum (ER) and the Golgi apparatus. This compartmentalization was first recognized about thirty years ago, and the current review not only updates studies on the compartmentalization of sphingolipid biosynthesis, but also discusses the ramifications of this feature for our understanding of how the pathway could have evolved. Thus, we augment some of our recent studies by inclusion of two further molecular pathways that need to be considered when analyzing the evolutionary requirements for generation of sphingolipids, namely contact sites between the ER and the Golgi apparatus, and the mechanism(s) of vesicular transport between these two organelles. Along with evolution of the individual enzymes of the pathway, their subcellular localization, and the supply of essential metabolites via the anteome, it becomes apparent that current models to describe evolution of the sphingolipid biosynthetic pathway may need substantial refinement.