Journal Article

Structural and functional consequences of reversible lipid asymmetry in living membranes

Doktorova, Milka, Symons, Jessica L., Levental, Ilya

2020

Overview

Maintenance of lipid asymmetry across the two leaflets of the plasma membrane (PM) bilayer is a ubiquitous feature of eukaryotic cells. Loss of this asymmetry has been widely associated with cell death. However, increasing evidence points to the physiological importance of non-apoptotic, transient changes in PM asymmetry. Such transient scrambling events are associated with a range of biological functions, including intercellular communication and intracellular signaling. Thus, regulation of interleaflet lipid distribution in the PM is a broadly important but underappreciated cellular process with key physiological and structural consequences. Here, we compile the mounting evidence revealing multifaceted, functional roles of PM asymmetry and transient loss thereof. We discuss the consequences of reversible asymmetry on PM structure, biophysical properties and interleaflet coupling. We argue that despite widespread recognition of broad aspects of membrane asymmetry, its importance in cell biology demands more in-depth investigation of its features, regulation, and physiological and pathological implications. The asymmetric distribution of lipids, including cholesterol, in biological membranes established actively by flippases and scramblases has structural, biophysical and functional consequences in cells and implications for communication across membranes.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 631/45/608 / 631/57 / 631/80/313 / 631/92/287/1192 / 631/92/314 / Animals / Apoptosis / Asymmetry / Biochemical Engineering / Biochemistry / Biological membranes / Bioorganic Chemistry / Cell Biology / Cell Communication / Cell death / Cell Membrane - chemistry / Cell Membrane - metabolism / Cell signaling / Cellular structure / Chemistry / Chemistry and Materials Science / Chemistry/Food Science / Cholesterol / Cholesterol - chemistry / Cholesterol - metabolism / Erythrocytes - chemistry / Erythrocytes - metabolism / Humans / Intracellular signalling / Lipid Bilayers - chemistry / Lipid Bilayers - metabolism / Lipids / Mammals / Membranes / Neurons - chemistry / Neurons - metabolism / Phosphatidylcholines - chemistry / Phosphatidylcholines - metabolism / Phosphatidylethanolamines - chemistry / Phosphatidylethanolamines - metabolism / Phosphatidylinositols - chemistry / Phosphatidylinositols - metabolism / Phosphatidylserines - chemistry / Phosphatidylserines - metabolism / Physiology / Review Article / Signal Transduction / Skewed distributions / Sphingomyelins - chemistry / Sphingomyelins - metabolism / Structure-function relationships