Mastrototaro L¹, Smorodchenko A², Aschenbach JR¹, Kolisek M³, Sponder G¹

¹ Institut für Veterinär-Physiologie, Freie Universität Berlin, Oertzenweg 19b, Berlin
² Charité Centrum Grundlagenmedizin CC 2, Institut für Vegetative Anatomie, Berlin
³ BioMed Martin, Jessenius Medical faculty, Commenius University, Martin, Slovakia

Cellular magnesium homeostasis is regulated by active balancing of Mg²⁺ uptake, intracellular Mg²⁺ storage and
Mg²⁺ efflux. Mg²⁺ transport across the plasma membrane is relatively well investigated. Several proteins were
characterized as channels or transporters mediating the uptake of Mg²⁺ (e.g. TRPM6/7, NIPA1 and MagT1) or
its extrusion (SLC41A1) across the plasma membrane. However, our knowledge about Mg²⁺ transport
mechanisms of subcellular compartments such as mitochondria is still modest.
We have characterized member A3 of the solute carrier family 41 (SLC41A3) as a mitochondrial Mg²⁺ export
system. Despite displaying significant homology to the well characterized Na⁺/Mg²⁺ exchanger SLC41A1 of the
plasma membrane, SLC41A3 does not mediate influx or efflux of Mg²⁺ across the plasma membrane. Confocal
immunofluorescence microscopy and subcellular fractionation confirmed that the protein is rather targeted to
mitochondria. Mitochondria of HEK293 cells overexpressing SLC41A3 exhibit a 60% increase in the extrusion of
Mg²⁺ compared with control cells not overexpressing the protein. This efflux mechanism is Na⁺-dependent and
temperature sensitive. These data identify SLC41A3 as a strong candidate for the first mammalian Mg²⁺
exporter of mitochondria.