Control of membrane lipid homeostasis by lipid-bilayer associated sensors: A mechanism conserved from bacteria to humans.

Abstract

The lipid composition of biological membranes is key for cell viability. Nevertheless, and despite their central role in cell function, our understanding of membrane physiology continues to lag behind most other aspects of cell biology. The maintenance of membrane properties in situations of environmental stress requires homeostatic sense-and-response mechanisms. For example, the balance between esterified saturated (SFAs) and unsaturated fatty acids (UFAs), is a key factor determining lipid packing, water permeability, and membrane fluidity. The reduced thermal motion of lipid acyl chains triggered by an increase in SFAs causes a tighter lipid packing and increase the membrane viscosity. Conversely almost all organisms adapt to membrane rigidifying conditions, such as low temperature in poikilotherms, by incorporating more lipids with poorly packing unsaturated acyl chains. The molecular mechanisms underlying membrane homeostasis are only starting to emerge through combinations of genetics, cell biology, lipidomics, structural approaches and computational modelling. In this review we discuss recent advances in defining molecular machineries responsible for sensing membrane properties and mediating homeostatic responses in bacteria, yeast and animals. Although these organisms use remarkably distinct sensing mechanisms to mediate membrane adaptation, they suggest that the principle of transmembrane signaling to integrate membrane composition with lipid biosynthesis is ancient and essential for life.