Biological Fractionation of Lithium Isotopes by Cellular Na+/H+ Exchangers Unravels Fundamental Transport Mechanisms
iScience(2023)
Abstract
Lithium (Li) has a wide range of uses in science, medicine, and industry, but its isotopy is underexplored, except in nuclear science and in geoscience. Li-6 and Li-7 isotopic ratio exhibits the second largest variation on earth's surface and constitutes a widely used tool for reconstructing past oceans and climates. As large variations have been measured in mammalian organs, plants or marine species, and as Li-6 elicits stronger effects than natural Li (similar to 95% Li-7), a central issue is the identification and quantification of biological influence of Li isotopes distribution. We show that membrane ion channels and Na+-Li+/H+ exchangers (NHEs) fractionate Li isotopes. This systematic Li-6 enrichment is driven by membrane potential for channels, and by intracellular pH for NHEs, where it displays cooperativity, a hallmark of dimeric transport. Evidencing that transport proteins discriminate between isotopes differing by one neutron opens new avenues for transport mechanisms, Liphysiology, and paleoenvironments.
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