Solute carrier 41A3 encodes for a mitochondrial Mg(2+) efflux system.
The important role of magnesium (Mg(2+)) in normal cellular physiology requires flexible, yet tightly regulated, intracellular Mg(2+) homeostasis (IMH). However, only little is known about Mg(2+) transporters of subcellular compartments such as mitochondria, despite their obvious importance for the deposition and reposition of intracellular Mg(2+) pools. In particular, knowledge about mechanisms responsible for extrusion of Mg(2+) from mitochondria is lacking. Based on circumstantial evidence, two possible mechanisms of Mg(2+) release from mitochondria were predicted: (1) Mg(2+) efflux coupled to ATP translocation via the ATP-Mg/Pi carrier, and (2) Mg(2+) efflux via a H(+)/Mg(2+) exchanger. Regardless, the identity of the H(+)-coupled Mg(2+) efflux system is unknown. We demonstrate here that member A3 of solute carrier (SLC) family 41 is a mitochondrial Mg(2+) efflux system. Mitochondria of HEK293 cells overexpressing SLC41A3 exhibit a 60% increase in the extrusion of Mg(2+) compared with control cells. This efflux mechanism is Na(+)-dependent and temperature sensitive. Our data identify SLC41A3 as the first mammalian mitochondrial Mg(2+) efflux system, which greatly enhances our understanding of intracellular Mg(2+) homeostasis.
Institute of Veterinary-Physiology, Free University of Berlin, Oertzenweg 19b, Berlin, D-14163, Germany.
Lucia
L
Mastrototaro
Institute of Vegetative Anatomy, Charité, Universitätsmedizin Berlin, Campus Charité-Mitte, Berlin, D-10117, Germany.
Alina
A
Smorodchenko
Institute of Veterinary-Physiology, Free University of Berlin, Oertzenweg 19b, Berlin, D-14163, Germany.
Jörg R
JR
Aschenbach
Institute of Veterinary-Physiology, Free University of Berlin, Oertzenweg 19b, Berlin, D-14163, Germany.
Martin
M
Kolisek
Institute of Veterinary-Physiology, Free University of Berlin, Oertzenweg 19b, Berlin, D-14163, Germany.
Gerhard
G
Sponder
D000255:Adenosine Triphosphate / Q000378:metabolism; D027241:Amino Acid Transport System y+L / Q000235:genetics* / Q000378:metabolism*; D003001:Cloning, Molecular; D057809:HEK293 Cells; D006801:Humans; D008274:Magnesium / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism; D013696:Temperature
D027241:Amino Acid Transport System y+L; D024101:Mitochondrial Proteins; D009363:Neoplasm Proteins; C115131:SLC43A1 protein, human; D000255:Adenosine Triphosphate; D012964:Sodium; D008274:Magnesium