Structural and functional consequences of reversible lipid asymmetry in living membranes

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

doi:10.1038/s41589-020-00688-0

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Structural and functional consequences of reversible lipid asymmetry in living membranes

Author(s): Milka Doktorova , Jessica L. Symons , Ilya Levental

Publication date (Electronic): November 16 2020

Journal: Nature Chemical Biology

Publisher: Springer Science and Business Media LLC

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Abstract

<p class="first" id="P1">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 the PM’s interleaflet lipid distribution 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 ensuing 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, as well as physiological and pathological implications. </p>

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Most cited references 92

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Microglia, the brain's professional phagocytes, can remove dead and dying neurons as well as synapses and the processes of live neurons. However, we and others have recently shown that microglia can also execute neuronal death by phagocytosing stressed-but-viable neurons - a process that we have termed phagoptosis. In this Progress article, we discuss evidence suggesting that phagoptosis may contribute to neuronal loss during brain development, inflammation, ischaemia and neurodegeneration.