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

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. 6Li and 7Li isotopic ratio exhibits the second largest variation on Earth 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 6Li elicits stronger effects than natural Li (~95% 7Li) 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 6Li 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.

Lithium isotopes in marine food webs: Effect of ecological and environmental parameters

“…It is known that active transporters present in all living organisms play a key role in the Li transfer to cells and organs (Counillon et al, 2016). Kinetic biological Li isotope fractionation have recently been highlighted (Thibon et al, 2021a;Poet et al, 2022) during active Li transfer, along with the intracellular pH and Na regulation, which influences the Li levels in cells and in specific organs (e.g., kidneys, brain). When considering only bivalves and fish from the Bay of Biscay, the combination of Li concentrations and Li isotopes allows to fully discriminate tissues (Figure 4), which strongly suggests that Li is involved in distinct paths and functions among these internal components.…”