Mechanisms of glycerophospholipid homeostasis in mammalian cells

Abstract

The membranes of mammalian cells contain hundreds of different phospholipid species, a variety of glycolipids and cholesterol. While the reasons for such compositional diversity are not well established, they probably relate to a multitude of membrane-associated functions each of which sets specific requirements for the chemical and physical properties of membranes. The lipid composition of membranes must therefore be accurately controlled. The maintenance of phospholipid homeostasis in a mammalian cell is a daunting task due to presence of many phospholipid (and other lipid) classes and hundreds of different molecular species. In addition, the phospholipid composition of the cellular membranes depends on several different phenomena including biosynthesis, remodelling, degradation and interorganelle trafficking. Accordingly, it is not surprising that phospholipid homeostasis in mammalian cells is poorly understood. Particularly little is known about the regulation and coordination of processes contributing to homeostasis. Nevertheless, it has become obvious that selective degradation plays a major role, albeit the enzymes involved remain to be discovered. Beside the complexity of the phenomenon, methodological limitations have hampered the progress in this field. Here, we review the key features of the processes contributing to phospholipid homeostasis in mammalian cells, with a particular emphasis on the regulation and coordination of biosynthesis and degradation.