Biological fractionation of lithium isotopes by cellular Na + /H + exchangers unravels fundamental transport mechanisms

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SUMMARY 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. 6 Li and 7 Li 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 6 Li elicits stronger effects than natural Li (~95% 7 Li) a central issue is the identification and quantification of biological influence of Li isotopes distribution. We show here that membrane ion channels and Na + -Li + /H + exchangers (NHEs), strongly fractionate Li isotopes. This systematic 6 Li 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, Li physiology, and paleoenvironments.

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