Biological fractionation of lithium isotopes by cellular Na+/H+ exchangers unravels fundamental transport mechanisms
Mallorie Poet,
Nathalie Vigier,
Yann Bouret,
Gisèle Jarretou,
Romain Gautier,
Saïd Bendahhou,
Vincent Balter,
Maryline Montanes,
Fanny Thibon,
Laurent Counillon
Affiliations
Mallorie Poet
Université Côte d’Azur, CNRS, Laboratoire de Physiomédecine Moléculaire (LP2M), Laboratories of Excellence Ion Channel Science and Therapeutics, Nice, France
Nathalie Vigier
Oceanography Laboratory of Villefranche (LOV, IMEV), CNRS, Sorbonne University, Villefranche-sur-Mer, France
Yann Bouret
Université Côte d’Azur, CNRS, Institut de Physique de Nice (INPHYNI), Nice, France; École Normale Supérieure de Lyon, CNRS, Laboratoire de Géologie de Lyon, Lyon, France
Gisèle Jarretou
Université Côte d’Azur, CNRS, Laboratoire de Physiomédecine Moléculaire (LP2M), Laboratories of Excellence Ion Channel Science and Therapeutics, Nice, France
Romain Gautier
Université Côte d’Azur, CNRS, Institut de Pharmacologie Moléculaire et Cellulaire (IPMC), Valbonne, France
Saïd Bendahhou
Université Côte d’Azur, CNRS, Laboratoire de Physiomédecine Moléculaire (LP2M), Laboratories of Excellence Ion Channel Science and Therapeutics, Nice, France
Vincent Balter
École Normale Supérieure de Lyon, CNRS, Laboratoire de Géologie de Lyon, Lyon, France
Maryline Montanes
Oceanography Laboratory of Villefranche (LOV, IMEV), CNRS, Sorbonne University, Villefranche-sur-Mer, France
Fanny Thibon
Oceanography Laboratory of Villefranche (LOV, IMEV), CNRS, Sorbonne University, Villefranche-sur-Mer, France
Laurent Counillon
Université Côte d’Azur, CNRS, Laboratoire de Physiomédecine Moléculaire (LP2M), Laboratories of Excellence Ion Channel Science and Therapeutics, Nice, France; Corresponding author
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. 6Li and 7Li 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 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 that membrane ion channels and Na+-Li+/H+ exchangers (NHEs) 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.
